Startseite Naturwissenschaften Phenylboronic acid-decorated polymeric nanomaterials for advanced bio-application
Artikel Open Access

Phenylboronic acid-decorated polymeric nanomaterials for advanced bio-application

  • Tianyu Lan und Qianqian Guo EMAIL logo
Veröffentlicht/Copyright: 31. Dezember 2019
Artikel downloaden (PDF)
Veröffentlichen auch Sie bei De Gruyter Brill
Manuskript einreichen Informationen für Autor*innen
Nanotechnology Reviews
Aus der Zeitschrift Nanotechnology Reviews Band 8 Heft 1

Abstract

The paradigm of using phenylboronic acid-decorated polymeric nanomaterials for advanced bio-application has been well established over the past decade. Phenylboronic acid and its derivatives are known to form reversible complexes with polyols, including sugar, diol and diphenol. This unique chemistry of phenylboronic acid has given many chances to be exploited for diagnostic and therapeutic applications. This review highlights the recent advances in fabrication of phenylboronic acid-decorated polymeric nanomaterials, especially focus on the interactions with glucose and sialic acid. Applications of these phenylboronic acid-decorated nanomaterials in drug delivery systems and biosensors are discussed.

Keywords: Phenylboronic acid; Polymeric nanomaterials; Polyols; Drug delivery

1 Introduction

Phenylboronic acid (PBA) and its derivatives are known to reversibly form cyclic boronic esters with polyol compounds [1, 2], hence they could recognize carbohydrates, such as glucose in blood and sialic acid (SA) on cancer cells. Carbohydrates are the foundation of life and play irreplaceable roles in a variety of cellular events, including proliferation, recognition, intercellular communication and immunoregulation. When disease occurs, the type and expression amount of carbohydrates would change. The unique chemistry of PBA with polyol compounds, especially carbohydrates, provides a way to design PBA-based polymeric nanomaterials. As polymeric nanomaterials could greatly enhance molecular interactions by multivalent effects, they have attracted much attention in biomedical applications [3, 4, 5], such as drug delivery systems and biosensors for diagnosis and therapeutics of diseases [6].

The most typical application of PBA and its derivatives is focused on glucose-responsive materials to recognize blood glucose and delivery insulin for the treatment of diabetes mellitus [7, 8, 9, 10]. However, PBA-based glucose-responsive materials could only work in alkaline media but not at physiological pH, due to the high pKa value (pKa > 8.0) of PBA moiety [11, 12, 13, 14].Numerous investigations have been focused on the design and synthesis of PBA-based polymers to decrease pKa of PBA moiety and increase the glucose-sensitivity as well as effectively release insulin at physiological pH [15, 16, 17, 18]. Interestingly, PBA and its derivatives can stably bind with SA in acid conditions, such as tumor acid microenvironment, resulting in another application of PBA-based polymeric nanomaterials to construct anticancer drugs delivery systems [19, 20, 21].

Herein, we review the recent advances in fabrication of PBA-decorated polymeric nanomaterials based on the specific interactions with carbohydrates, and highlight the biomedical applications in drug delivery systems and biosensors.

2 PBA-based glucose-sensitive polymeric nanomaterials

Insulin-dependent diabetes mellitus characterized by accumulating glucose concentrations in blood has been a major global health epidemic [22, 23], leading to a highly need to design glucose-responsive materials for self-regulated insulin release responding to the variation of blood glucose concentrations. PBA-based glucose-responsive polymeric materials have been well-investigated because they are versatile enough to design different formulations and more stable than protein-based systems (glucose oxidase and concanavalin A)[24]. The interaction between PBA and glucose is reversible equilibrium, which lays the foundation for the glucose-responsiveness of PBA-based materials. PBA-based glucose-sensitive nanomaterials could be fabricated by different approaches, such as self-assembly of amphiphilic copolymers, polymerizing into nano/microgels, and conjugating with inorganic hybrid nanoparticles, etc. [25, 26, 27, 28, 29, 30, 31].

As most of the PBA-based materials reported demonstrate maximum glucose-sensitivity at pH 9 ~ 10, significant efforts have been focused on decreasing their pKa values and enhancing the sensitivity to glucose at physiological conditions. Sumerlin group prepared macromolecular stars with boronic ester linkages to self-assemble into nanoparticles [25]. The boronic esters were formed between 3-acrylamidophenyl boronic acid (APBA) and mono-functional diols, and the formation-dissociation process was proved to be repeatable over multiple cycles (Figure 1A). Later, they synthesized another boronic acid-based polymeric aggregations with glucose-sensitivity at pH = 7.4, indicating promising prospects for controlled insulin delivery systems under physiological conditions (Figure 1B) [26]. Kim group prepared two kinds of insulin-loaded polymersomes from polyboroxole-based block copolymers, which could release insulin responding to the glucose-triggered disassembly under physiologically conditions (see Figure 2) [28, 29]. Differently, Yao et al. designed a novel nanocarrier with phenylboronate ester as a leaving group in the hydrophobic block, and the nanocarrier successfully realized glucose-responsiveness and insulin release at neutral pH (Figure 3) [27].

Figure 1 (A) Formation and disintegration of dynamic-covalent nanoaggregates via boronic ester linkages. Reprinted with permission from [25]. Copyright 2011, American Chemical Society. (B) Schematic illustration for glucose-triggered dissociation of the nanoparticles. Reprinted with permission from [26]. Copyright 2012, American Chemical Society
Figure 1

(A) Formation and disintegration of dynamic-covalent nanoaggregates via boronic ester linkages. Reprinted with permission from [25]. Copyright 2011, American Chemical Society. (B) Schematic illustration for glucose-triggered dissociation of the nanoparticles. Reprinted with permission from [26]. Copyright 2012, American Chemical Society

Figure 2 (A) Self-assembly of PEG-b-PBOx polymersome and its disassembly responding to monosaccharides. Reprinted with permission from [28]. Copyright 2012, American Chemical Society. (B) Schematic illustration for self-assembly and glucose-responsive disassembly of polymersomes. Reprinted with permission from [29]. Copyright 2012, American Chemical Society
Figure 2

(A) Self-assembly of PEG-b-PBOx polymersome and its disassembly responding to monosaccharides. Reprinted with permission from [28]. Copyright 2012, American Chemical Society. (B) Schematic illustration for self-assembly and glucose-responsive disassembly of polymersomes. Reprinted with permission from [29]. Copyright 2012, American Chemical Society

Figure 3 Schematic illustration for sugar-responsive behavior of nanoassembly. Reproduced with permission from [27]. Copyright 2011, The Royal Society of Chemistry
Figure 3

Schematic illustration for sugar-responsive behavior of nanoassembly. Reproduced with permission from [27]. Copyright 2011, The Royal Society of Chemistry

In recent years, Zhang group synthesized a series of PBA-based amphiphilic copolymers by radical polymerization and living/controlled polymerization to delivery insulin at physiological conditions [32, 33, 34, 35, 36, 37]. By introducing carbohydrate moieties into copolymers, pKa values of PBA moieties were decreased and glucose sensitivity was enhanced at physiological conditions, which ensured the delivery effectiveness and self-regulated release of insulin. To explore the effect of polymer structures on self-assembled aggregates and glucose-sensitivity, a series of amphiphilic block and random PBA-based copolymers with similar monomer compositions were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization [38]. These copolymers could easily self-assemble into spherically shaped nanoparticles in aqueous solution and two types of nanoparticles facilitated insulin delivery at physiological pH, despite insulin release rate of random copolymer was slightly quicker than that of the block ones (Figure 4).

Figure 4 Schematic illustration for the self-assembly and insulin release behaviors of block and random copolymeric nanoparticles. Adapted with permission from [38]. Copyright 2015, American Chemical Society
Figure 4

Schematic illustration for the self-assembly and insulin release behaviors of block and random copolymeric nanoparticles. Adapted with permission from [38]. Copyright 2015, American Chemical Society

Besides PBA-based amphiphilic copolymers self-assembling into nanoparticles, the chemically cross-linked PBA-decorated nanogels (microgels) also attract much attention because they can meet different needs, such as prompt drug delivery, oral administration, and intravenous injection. Typical PBA-based glucose-responsive nanogels were prepared through modification of poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAM-co-AA)] with 3-amino-phenylboronic acid (Figure 5) [39, 40, 41]. The introduction of PBA groups significantly decreased volume phase transition temperature of microgels, yet a pH value higher than 7.4 was needed to release loaded-insulin in response to glucose.

Figure 5 Synthesis of glucose-sensitive P(NIPAM-PBA) microgels with pendant 3-amino-phenylboronic acid. Adapted with permission from [41]. Copyright 2006, American Chemical Society
Figure 5

Synthesis of glucose-sensitive P(NIPAM-PBA) microgels with pendant 3-amino-phenylboronic acid. Adapted with permission from [41]. Copyright 2006, American Chemical Society

Wang et al. reported multifunctional microgels based on PNIPAM, N-acryloyl-3-aminophenylboronic acid and two fluorescent molecules [42]. The FRET efficiencies and shrink-swelling properties of microgels could be tuned via thermo-induced collapse or glucose-induced swelling at proper pH and temperature (Figure 6). Tang et al. synthesized a specific glucose-sensitive P(NIPAM-AAPBA) microgel that displayed specific glucose sensitivity at physiological pH [43]. Due to the interference from fructose, galactose, and lactate was negligible, the author considered the contraction-type specific glucose-sensitive microgels had potential applications in self-regulated insulin delivery and glucose sensing (Figure 7). Zhao et al. prepared a novel nanogel with high glucose sensitivity through one-pot thiol-ene copolymerization of pentaerythritol tetra(3-mercaptopropionate), poly(ethylene glycol) diacrylate, methoxyl poly(ethylene glycol) acrylate and N-acryloyl-3-aminophenylboronic acid [44]. The release of loaded-insulin was triggered and modulated at pH 7.4 responding to different glucose concentrations (Figure 8).

Figure 6 Synthesis and modulation of FRET efficiencies for microgels by temperature variations and adding glucose. Reprinted with permission from [42]. Copyright 2011, American Chemical Society
Figure 6

Synthesis and modulation of FRET efficiencies for microgels by temperature variations and adding glucose. Reprinted with permission from [42]. Copyright 2011, American Chemical Society

Figure 7 The complexation equilibrium between glucose and PBA groups, and the glucose-induced swelling of P(NIPAM-AAPBA) microgels. Reproduced with permission from [43]. Copyright 2014, The Royal Society of Chemistry
Figure 7

The complexation equilibrium between glucose and PBA groups, and the glucose-induced swelling of P(NIPAM-AAPBA) microgels. Reproduced with permission from [43]. Copyright 2014, The Royal Society of Chemistry

Figure 8 Structures of nanogels and glucose-sensitive behaviors of ARS-loaded nanogels in PBS [44]. Reprinted with permission from [44]. Copyright 2013, Elsevier
Figure 8

Structures of nanogels and glucose-sensitive behaviors of ARS-loaded nanogels in PBS [44]. Reprinted with permission from [44]. Copyright 2013, Elsevier

To simultaneously achieve optical detection of glucose, high drug loading capacity, and self-regulated drug delivery, Wu and coauthors reported a series of PBA-based hybrid microgels with glucose-sensitivity to realize self-regulated insulin delivery at physiological pH [16]. The multifunctional hybrid nanogels were made of Ag nanoparticle cores covered with a copolymer gel shell of poly(4-vinylphenylboronicacid-co-2-(dimethylamino)ethylacrylate) [p(VPBA-DMAEA)] [16, 45, 46, 47]. The small sized Ag cores (10 ± 3 nm) in microgels provided fluorescence as an optical code. The microgels could not only convert the disruption in homeostasis of glucose level into optical signals to detect the blood glucose levels, but also regulate release of preloaded insulin responding to the glucose level variations (Figure 9A). Later, they reported a fluorescent responsive hybrid nanogel of Zinc oxide@poly[N-isopropylacrylamide (NIPAM)-acrylamide (AAm)-2-aminomethyl-5-fluorophenylboronic acid (FPBA)] [45]. The hybrid nanogels could sensitively and selectively detect glucose via fluorescent signals over the clinically relevant glucose concentrations of 18-540 mg/dl. The nanogels could also regulate loaded-insulin release behaviors in response to different glucose levels and exhibit quicker release rate at higher glucose level (Figure 9B).

Figure 9 (A) Smart hybrid nanogels for integration of optical glucose detection and self-regulated insulin delivery into a single nano-object. Reprinted with permission from [16]. Copyright 2010 American Chemical Society. (B) A single hybrid nanogel for integration of fluorescent glucose sensing and insulin delivery. Reprinted with permission from [45]. Copyright 2012, SAGE Publications
Figure 9

(A) Smart hybrid nanogels for integration of optical glucose detection and self-regulated insulin delivery into a single nano-object. Reprinted with permission from [16]. Copyright 2010 American Chemical Society. (B) A single hybrid nanogel for integration of fluorescent glucose sensing and insulin delivery. Reprinted with permission from [45]. Copyright 2012, SAGE Publications

3 PBA-mediated SA recognition on cancer cells

SA is an anionic monosaccharide that frequently occurs at the termini of glycan chains. Its overexpression on cell membranes implicated in the malignant and metastatic phenotypes of various types of cancers, such as lung, breast, colon, prostate, bladder, and stomach cancer [48, 49]. Thus, advanced techniques to monitor SA expression would have great significance on diagnosis and therapeutics. Interestingly, PBA and its derivatives can recognize SA and form the stable boronic ester with SA not only in the physiological and basic pH but even in acidic medium such as tumor acidic microenvironment [50, 51]. Thus, many researchers have devoted to explore the advanced materials based on PBA-mediated SA-recognition as cancer diagnostic and therapeutic agents [52, 53, 54, 55, 56, 57, 58]. Matsumoto et al. prepared a PBA modified monolayer gold electrode to noninvasively detect SA on cell membranes [52]. Deng et al. prepared glucose-bridged and 4-mercaptophenyl boronic acid-decorated silver nanoparticle (Glucose-MPBA@AgNPs) as nanoprobe for highly sensitive recognition of SA expression levels on the surfaces of both normal and cancer cells via surface-enhanced raman scattering spectroscopy (Figure 10) [54].

Figure 10 Targeted identification of the cancer cell by a highly sensitive Glucose-MPBA@AgNPs nanoprobes. Reprinted with permission from [54]. Copyright 2017, Elsevier
Figure 10

Targeted identification of the cancer cell by a highly sensitive Glucose-MPBA@AgNPs nanoprobes. Reprinted with permission from [54]. Copyright 2017, Elsevier

Among these materials, polymeric nanoparticles occupy the dominant roles owing to their excellent expression in the cancer diagnostic and therapeutic fields [59, 60, 61, 62, 63]. Liu et al. prepared PBA and amphiphilic copolymer of maleic anhydride/octadecene coated with semiconductor quantum dots as imaging probes to specifically label SA on living cells [62]. These probes could one-step label and continuously track SA moieties on cell surfaces without any pretreatment of living cells (Figure 11). Zhang et al. prepared a SA-recognition system based on gold nanoparticles (AuNPs) labeled on biotinylated phenylboronic acid (biotin-APBA), in which AuNPs enabled to enhance signal in an inductively coupled plasma mass spectrometry [63]. By taking HepG2 and MCF-7 cells as model cancer cells, the average numbers of SA expressed on the single MCF-7 and HepG2 cell surface were 7.0 × 109 and 5.4 × 109, respectively. The method is helpful to study tumor malignancy and metastasis for biological research and clinical diagnostics (Figure 12).

Figure 11 Specific binding of QD with SA on living cells at the C-8,9 diol of SA. Reprinted with permission from [62]. Copyright 2011, American Chemical Society
Figure 11

Specific binding of QD with SA on living cells at the C-8,9 diol of SA. Reprinted with permission from [62]. Copyright 2011, American Chemical Society

Figure 12 Illustration for recognition of SA on the cell surface assay. Reproduced with permission from [63]. Copyright 2016, The Royal Society of Chemistry
Figure 12

Illustration for recognition of SA on the cell surface assay. Reproduced with permission from [63]. Copyright 2016, The Royal Society of Chemistry

In recent years, polymeric nanoparticles with different architectures and formulations as drug delivery carriers based on PBA-SA recognition for cancer therapeutics were investigated by many researchers [55, 56, 57, 64]. Deshayes et al. prepared PBA-installed polymeric micelles to target sialylated epitopes overexpressed on cancer cells, and the micelles showed high affinity for SA even under intratumoral pH conditions, suggesting the potential application of PBA-installed nanocarriers for enhanced tumor targeting (Figure 13) [55]. Zhao et al. developed PBA-terminated polyethylene glycol monostearate (PBA-PEG-C18) and pluronic P123 (PEG20-PPG70-PEG20) targeting drug delivery system based on the selective binding with PBA [64]. Different from others’ work, herein PBA located on micelles margin was protected by fructose to avoid nonspecific interaction with normal cells or other components containing cis-diol residues in vivo circulation (Figure 14).

Figure 13 Preparation of PBA-installed DACHPt-loaded micelles by self-assembly of polymer-metal complex in distilled water. PBA moieties on the surface of micelles can bind to SA. Reprinted with permission from [55]. Copyright 2013, American Chemical Society
Figure 13

Preparation of PBA-installed DACHPt-loaded micelles by self-assembly of polymer-metal complex in distilled water. PBA moieties on the surface of micelles can bind to SA. Reprinted with permission from [55]. Copyright 2013, American Chemical Society

Figure 14 Illustration of pH-activated targeting drug delivery system based on selective binding with PBA. Reprinted with permission from [64]. Copyright 2016, American Chemical Society
Figure 14

Illustration of pH-activated targeting drug delivery system based on selective binding with PBA. Reprinted with permission from [64]. Copyright 2016, American Chemical Society

Besides synthetic polymers, PBA could also be decorated on the natural polymers for specific targeting SA on cancer cells [65, 66, 67]. Lee et al. prepared nanoparticles based on (3-aminomethylphenyl)boronic acid (AMPB)-functionalized chondroitin sulfate A (CSA)–deoxycholic-acid (DOCA) to enhance tumor targeting and penetration [65]. Near-infrared fluorescence imaging revealed that CSA–DOCA–AMPB nanoparticles could target and penetrate into tumor based on both CSA–CD44 receptor and boronic acid–SA interactions. Multiple intravenous injections of DOX-loaded CSA–DOCA–AMPB nanoparticles efficiently inhibited the growth of A549 tumor in xenografted mouse models. These boronic acid-rich nanoparticles are promising candidates for cancer therapy and imaging (Figure 15). Jeong et al. fabricated AMPB-installed hyaluronic acid–ceramide (HACE)-based nanoparticles for tumor-targeted delivery [66]. HACE-AMPB/MB nanoparticles improved cellular accumulation efficiency, tumor penetration efficiency, and antitumor efficacy, indicating the PBA-SA interaction played important roles in augmented tumor targeting and penetration (Figure 16).

Figure 15 Schematic illustration of tumor targeting and penetrating action of CSA-DOCA-AMPB/DOX nanoparticles. Reproduced with permission from [65]. Copyright 2018, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Figure 15

Schematic illustration of tumor targeting and penetrating action of CSA-DOCA-AMPB/DOX nanoparticles. Reproduced with permission from [65]. Copyright 2018, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Figure 16 The tumor targeting and penetration strategy using HACE-AMPB/MB nanoparticles. Reprinted with permission from [66]. Copyright 2017, Elsevier
Figure 16

The tumor targeting and penetration strategy using HACE-AMPB/MB nanoparticles. Reprinted with permission from [66]. Copyright 2017, Elsevier

PBA-based polymeric nanoparticles could also be used to deliver siRNA for cancer therapy [68, 69]. Ji et al. made PBA conjugated onto low molecular weight polyethylenimine (PEI) to generate amphiphilic PBA-grafted PEI (PEI-PBA) [68]. PEI-PBA and siRNA spontaneously self-assembled into PEI-PBA/siRNA nanocomplexes that dramatically increased siRNA uptake up to 70 - 90% in several cancer cell lines due to the PBA-SA interaction. Moreover, the PEI-PBA nanovector effectively promoted the lysosome escape of siRNA, thereby robustly induced tumor apoptosis and cell cycle arrest. Hence, SA-targeted PEI-PBA could be a highly efficient and safe nanovector to improve the efficacy of cancer siRNA therapy (Figure 17). Kim et al. also reported a PBA-based polymer architecture as gene carrier for targeting anti-angiogenic tumor [69]. The nanocarrier was obtained by crosslinking of low-molecular-weight (MW) PEI to form high-MW PEI based on the interaction between PBA and galactose, resulting in strong interaction with anionic DNA. Inside the tumor cells, the linkages of PBA and sugar were disrupted by either acidic endosomal pH or intracellular ATP, resulting in effective release of preloaded gene (Figure 18). Wang et al. developed PBA-mediated chitosan nanoparticles for tumor targeting, and the results showed that PBA-decorated nanoparticles were more easily internalized by tumor cells compared to non-decorated nanoparticles in 2-D and 3-D cell models, indicating a potential application for delivering more drugs into tumor cells due to the active targeting effect of boronic acid groups [67].

Figure 17 Synthesis of PEI-PBA conjugates for SA-targeted siRNA delivery. Reprinted with permission from [68]. Copyright 2016, American Chemical Society
Figure 17

Synthesis of PEI-PBA conjugates for SA-targeted siRNA delivery. Reprinted with permission from [68]. Copyright 2016, American Chemical Society

Figure 18 Schematic illustration of anti-angiogenic gene delivery mediated by PBA-PEG-Cross PEI vector. Reprinted with permission from [69]. Copyright 2015, Elsevier
Figure 18

Schematic illustration of anti-angiogenic gene delivery mediated by PBA-PEG-Cross PEI vector. Reprinted with permission from [69]. Copyright 2015, Elsevier

4 Biosensor

Due to the binding capacity of PBA and its derivatives towards free sugars or sugar-protein complexes, they have been extensively investigated as the fundamental parts of biosensor systems. The most typical sensor is glucose-sensor for detecting blood glucose concentrations in diabetes [70, 71, 72, 73, 74, 75]. However, mostly of sensors were based on gold nanoparticles/surfaces owing to their plasmonic properties, PBA-based polymeric nanopartilcles used in the nanobiosensor were seldom explored. Zhou and coworkers developed PBA-decorated CdS QDs-immobilized p(NIPAM-AAm-PBA) microgels [71]. The microgels undergone swelling and deswelling process resulting in changes in the florescence intensity of QDs in response to different glucose concentrations (Figure 19). Yetisen et al. developed a PBA-decorated PA Am matrix-Ag0 nanoparticle system used as the clinically relevant optical glucose photonic nanosensor [74]. The nanosensor response was achieved within 5 min, reset to baseline in ~10 s, and could be reused at least 400 times without a compromise in accuracy. The sensor may have implications for reusable, equipment-free colorimetric point-of-care diagnostic devices for diabetes screening (Figure 20).

Figure 19 Reversible fluorescence quenching and anti-quenching of CdS QDs-immobilized p(NIPAM-AAm-PBA) microgels in response to different glucose concentrations. Reproduced with permission from [71]. Copyright 2009, The Royal Society of Chemistry
Figure 19

Reversible fluorescence quenching and anti-quenching of CdS QDs-immobilized p(NIPAM-AAm-PBA) microgels in response to different glucose concentrations. Reproduced with permission from [71]. Copyright 2009, The Royal Society of Chemistry

Figure 20 Illustration of the sensor for sensing the target glucose. Reprinted with permission from [74]. Copyright 2014, American Chemical Society
Figure 20

Illustration of the sensor for sensing the target glucose. Reprinted with permission from [74]. Copyright 2014, American Chemical Society

Besides detection of glucose, PBA-based sensors, though not the polymeric nanoparticle systems, could also detect SA [52, 76], glycoproteins [77, 78], bacteria [79, 80, 81] and virus [82, 83] based on the interaction between PBA and carbohydrates, indicating the great potential applications in the sensor fields.

5 Stimuli-responsive drug delivery systems

PBA and its derivatives can combine with cisdiol/diphenol, and the interactions are pH responsive to disassemble. Some PBA derivatives are hydrogen peroxide (H2O2) responsive to degrade. These properties of PBA and its derivatives could be applied in stimuli-responsive drug delivery systems.

5.1 Diols responsiveness

PBA can bind with a variety of cis-diols, such as galactose, mannose, glucose, 1,3-diols, etc. Their interactions are always pH responsive,which could be applied in the stimuli-responsive drug delivery systems [84, 85, 86]. Kim et al. formulated a water-soluble nanoconstruct by forming boronic ester between the cis-1,3-diol of andrographolide (AND) and hydrophilically polymerized phenylboronic acid (pPBA) [85]. Due to the pH- and diol-dependent affinity of boronic ester, AND release was regulated by low pH and high ATP concentrations. Besides, pPBA-AND nanoconstruct exhibited an excellent tumor targeting ability both in vitro and in vivo owing to the intrinsic property of PBA moieties (Figure 21).

Figure 21 Schematic illustration for the formulation and destruction of pPBA-AND nanoconstruct. Reprinted with permission from [85]. Copyright 2016, Elsevier
Figure 21

Schematic illustration for the formulation and destruction of pPBA-AND nanoconstruct. Reprinted with permission from [85]. Copyright 2016, Elsevier

5.2 Diphenol responsiveness

The pH-sensitive interaction between PBA and diphenol is always used in the stimuli-responsive drug delivery systems [87, 88, 89]. Li et al. developed a DOX-loaded fluorescent nanoparticle based on the installed boronic acid-modified poly(lactic acid)-poly(ethyleneimine)(PLA-PEI) copolymers for intracellular imaging and pH-responsive drug delivery [89]. DOX-loaded nanoparticles showed pH-responsive drug release and effectively suppressed the proliferation of MCF-7 cells. In addition, the fluorescent nanoparticles tracked the process of endosomal escape by real-time imaging (Figure 22).

Figure 22 Schematic illustration for the formulation of FBNPs-DOX nanoparticles and pH-responsive DOX release. Reproduced with permission from [89]. Copyright 2014, The Royal Society of Chemistry
Figure 22

Schematic illustration for the formulation of FBNPs-DOX nanoparticles and pH-responsive DOX release. Reproduced with permission from [89]. Copyright 2014, The Royal Society of Chemistry

5.3 H2O2 responsiveness

H2O2 is highly expressed in tumor site, this could be exploited in the design of H2O2-responsive drug delivery systems for cancer therapy. Interestingly, 4-(methylol) phenylboronic acid and its derivatives are H2O2-responsive to induce PBA disintegration and loaded-drug release [56, 90, 91]. Yu et al. recently designed a temperature and H2O2-responsive “nano-valve” of ROSP@MSN by taking advantage of mesoporous silica nanoparticles (MSN) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)benzyl acrylate modified polymers (ROSP) [91]. ROSP@MSN could achieve cargo loading drug in cold water, and subsequently close the pore by raising temperature to obtain ROSP@MSN@DOX. Upon the stimulus of H2O2, ROSP@MSN@DOX exhibited excellent DOX release behavior under physiological conditions (Figure 23).

Figure 23 Schematic illustration for the temperature and H2O2-responsive behaviors of ROSP@MSN@DOX nanoparticles in aqueous medium. Reprinted with permission from [91]. Copyright 2017, Elsevier
Figure 23

Schematic illustration for the temperature and H2O2-responsive behaviors of ROSP@MSN@DOX nanoparticles in aqueous medium. Reprinted with permission from [91]. Copyright 2017, Elsevier

6 Conclusion

In this paper, some new advances of PBA-based strategies for diagnostic and therapeutic applications are reviewed. Because of the versatility for different designs and the specific interactions with polyol compounds, PBA and its derivatives have been widely exploited in constructing glucose-responsive, SA-recognized and stimuli-responsive polymeric nanomaterials, such as drug delivery systems and biosensors. A series of progresses have been made in recent years including synthesis of new PBA-based polymers and fabrication of PBA-decorated nano-materials. These PBA-decorated materials are designed to operate upon the disease microenvironment characters, such as under physiological pH or tumor acid condition. Until now, most drug delivery systems based on PBA-decorated nanoparticles were focused on insulin and anticancer drugs aiming at treatment of diabetes mellitus and cancer, respectively. And most PBA-based biosensors were focused on blood glucose detection. In conclusion, PBA and its derivatives-decorated polymers and nanomaterials have great potential applications in smart drug delivery systems and biosensors for the diagnosis and therapeutics of diseases.

Acknowledgement

This work was supported by the Guizhou Provincial Department of Education Youth Science and Technology Talent Development Project (Grant no. [2018]150), the Doctoral Foundation of Guizhou Medical University (Grant no. JY2017-28), the Science and Technology Department of Guizhou Province, Guizhou Branch of Talent Gund (Grant no. [2017]5718).

  1. Conflict of Interest

    Conflict of Interests: The authors declare no conflict of interest regarding the publication of this paper.

References

[1] Lorand J.P., Edwards J.O., Polyol complexes and structure of the benzeneboronate ion, J. Org. Chem., 1959, 24, 769-774.10.1021/jo01088a011Suche in Google Scholar

[2] Van Duin M., Peters J.A., Kieboom A.P.G., Van Bekkum H., Studies on borate esters 1: The pH dependence of the stability of esters of boric acid and borate in aqueous medium as studied by 11B NMR, Tetrahedron, 1984, 40, 2901-2911.10.1016/S0040-4020(01)91300-6Suche in Google Scholar

[3] James T.D., Sandanayake K.R.A.S., Shinkai S., Saccharide sensing with molecular receptors based on boronic acid, Angew. Chem. Inter. Ed., 1996, 35, 1910-1922.10.1002/anie.199619101Suche in Google Scholar

[4] Cambre J.N., Roy D., Sumerlin B.S., Tuning the sugar-response of boronic acid block copolymers, J. Polym. Sci., Part A: Polym. Chem., 2012, 50, 3373-3382.10.1002/pola.26125Suche in Google Scholar

[5] Vogt A.P., Trouillet V., Greiner A.M., Kaupp M., Geckle U., Barner L., Hofe T., Barner-Kowollik C., A facile route to boronic acid functional polymeric microspheres via epoxide ring opening, Macromol. Rapid Comm., 2012, 33, 1108-1113.10.1002/marc.201200144Suche in Google Scholar PubMed

[6] Ting S.R.S., Chen G., Stenzel M.H., Synthesis of glycopolymers and their multivalent recognitions with lectins, Polym. Chem., 2010, 1, 1392-1412.10.1039/c0py00141dSuche in Google Scholar

[7] Ma R., Shi L., Phenylboronic acid-based glucose-responsive polymeric nanoparticles: Synthesis and applications in drug delivery, Polym. Chem., 2014, 5, 1503-1518.10.1039/C3PY01202FSuche in Google Scholar

[8] Jin X., Zhang X., Wu Z., Teng D., Zhang X., Wang Y., Wang Z., Li C., Amphiphilic random glycopolymer based on phenylboronic acid: Synthesis, characterization, and potential as glucose-sensitive matrix, Biomacromolecules, 2009, 10, 1337-1345.10.1021/bm8010006Suche in Google Scholar PubMed

[9] Wang B., Ma R., Liu G., Liu X., Gao Y., Shen J., An Y., Shi L., Effect of coordination on the glucose-responsiveness of PEG-b-(PAA-co-PAAPBA) micelles,Macromol. Rapid Comm., 2010, 31, 1628-1634.10.1002/marc.201000164Suche in Google Scholar PubMed

[10] Sun L., Zhang X., Wu Z., Zheng C., Li C., Oral glucose- and pH-sensitive nanocarriers for simulating insulin release in vivo, Polym. Chem., 2014, 5, 1999-2009.10.1039/C3PY01416ASuche in Google Scholar

[11] Kataoka K., Miyazaki H., Bunya M., Okano T., Sakurai Y., Totally synthetic polymer gels responding to external glucose concentration: Their preparation and application to on-off regulation of insulin release, J. Am. Chem. Soc., 1998, 120, 12694-12695.10.1021/ja982975dSuche in Google Scholar

[12] Hoare T., Pelton R., Engineering glucose swelling responses in poly(N-isopropylacrylamide)-based microgels, Macromolecules, 2007, 40, 670-678.10.1021/ma062254wSuche in Google Scholar

[13] Matsumoto A., Kurata T., Shiino D., Kataoka K., Swelling and shrinking kinetics of totally synthetic, glucose-responsive polymer gel bearing phenylborate derivative as a glucose-sensing moiety, Macromolecules, 2004, 37, 1502-1510.10.1021/ma035382iSuche in Google Scholar

[14] Guo H., Li H., Gao J., Zhao G., Ling L.,Wang B., Guo Q., Gu Y., Li C., Phenylboronic acid-based amphiphilic glycopolymeric nanocarriers for in vivo insulin delivery, Polym. Chem., 2016, 7, 3189-3199.10.1039/C6PY00131ASuche in Google Scholar

[15] Kim K.T., Cornelissen J.J.L.M., Nolte R.J.M., Hest J.C.M.V.,Polymeric monosaccharide receptors responsive at neutral pH, J. Am. Chem. Soc., 2009, 131, 13908-13909.10.1021/ja905652wSuche in Google Scholar PubMed

[16] Wu W., Mitra N., Yan E.C.Y., Zhou S.,Multifunctional hybrid nanogel for integration of optical glucose sensing and self-regulated insulin release at physiological pH, ACS Nano, 2010, 4, 4831-4839.10.1021/nn1008319Suche in Google Scholar PubMed

[17] Li Y., Xiao W., Xiao K., Berti L., Luo J., Tseng H.P., Fung G., Lam K.S., Well-defined, reversible boronate crosslinked nanocarriers for targeted drug delivery in response to acidic pH values and cis-diols, Angew. Chem. Int. Ed., 2012, 124, 2918-2923.10.1002/ange.201107144Suche in Google Scholar

[18] Matsumoto A., Ishii T., Nishida J., Matsumoto H., Kataoka K., Miyahara Y., A synthetic approach toward a self-regulated insulin delivery system, Angew. Chem. Int. Ed., 2012, 51, 2124-2128.10.1002/anie.201106252Suche in Google Scholar PubMed

[19] Lee C.-S., Kim S., Kim M., Ion-sensitive field-effect transistor for biological sensing, Sensors, 2009, 9, 7111-7131.10.3390/s90907111Suche in Google Scholar PubMed PubMed Central

[20] Geninatti Crich S., Alberti D., Szabo I., Aime S., Djanashvili K.,MRI visualization of melanoma cells by targeting overexpressed sialic acid with a GdIII-dota-en-pba imaging reporter, Angew. Chem. Int. Ed., 2013, 52, 1161-1164.10.1002/anie.201207131Suche in Google Scholar PubMed

[21] Sanjoh M., Miyahara Y., Kataoka K.,Matsumoto A., Phenylboronic acids-based diagnostic and therapeutic applications, Anal. Sci., 2014, 30, 111-117.10.2116/analsci.30.111Suche in Google Scholar PubMed

[22] Gu Z., Aimetti A.A., Wang Q., Dang T.T., Zhang Y., Veiseh O., Cheng H., Langer R.S., Anderson D.G., Injectable nano-network for glucose-mediated insulin delivery, ACS Nano, 2013, 7, 4194-4201.10.1021/nn400630xSuche in Google Scholar PubMed PubMed Central

[23] Zhao L., Xiao C., Wang L., Gai G., Ding J., Glucose-sensitive polymer nanoparticles for self-regulated drug delivery, Chem. Commun., 2016, 52, 7633-7652.10.1039/C6CC02202BSuche in Google Scholar PubMed

[24] Lapeyre V., Gosse I., Chevreux S., Ravaine V., Monodispersed glucose-responsive microgels operating at physiological salinity, Biomacromolecules, 2006, 7, 3356-3363.10.1021/bm060588nSuche in Google Scholar PubMed

[25] Bapat A.P., Roy D., Ray J.G., Savin D.A., Sumerlin B.S., Dynamic-covalentmacromolecular stars with boronic ester linkages, J. Am. Chem. Soc., 2011, 133, 19832-19838.10.1021/ja207005zSuche in Google Scholar PubMed

[26] Roy D., Sumerlin B.S., Glucose-sensitivity of boronic acid block copolymers at physiological pH, ACS Macro Lett., 2012, 1, 529-532.10.1021/mz300047cSuche in Google Scholar

[27] Yao Y., Wang X., Tan T., Yang J., A facile strategy for polymers to achieve glucose-responsive behavior at neutral pH, Soft Matter, 2011, 7, 7948-7951.10.1039/c1sm05978eSuche in Google Scholar

[28] Kim H., Kang Y.J., Kang S., Kim K.T.,Monosaccharide-responsive release of insulin from polymersomes of polyboroxole block copolymers at neutral pH, J. Am. Chem. Soc., 2012, 134, 4030-4033.10.1021/ja211728xSuche in Google Scholar PubMed

[29] Kim H., Kang Y.J., Jeong E.S., Kang S., Kim K.T., Glucose-responsive disassembly of polymersomes of sequence-specific boroxole-containing block copolymers under physiologically relevant conditions, ACS Macro Lett., 2012, 1, 1194-1198.10.1021/mz3004192Suche in Google Scholar

[30] Ma R., Yang H., Li Z., Liu G., Sun X., Liu X., An Y., Shi L., Phenylboronic acid-based complex micelles with enhanced glucose-responsiveness at physiological pH by complexation with glycopolymer, Biomacromolecules, 2012, 13, 3409-3417.10.1021/bm3012715Suche in Google Scholar PubMed

[31] Liu G., Ma R., Ren J., Li Z., Zhang H., Zhang Z., An Y., Shi L., A glucose-responsive complex polymeric micelle enabling repeated on-off release and insulin protection, Soft Matter, 2013, 9, 1636-1644.10.1039/C2SM26690CSuche in Google Scholar

[32] Zheng C., Guo Q., Wu Z., Sun L., Zhang Z., Li C., Zhang X., Amphiphilic glycopolymer nanoparticles as vehicles for nasal delivery of peptides and proteins, Eur. J. Pharm. Sci., 2013, 49, 474-482.10.1016/j.ejps.2013.04.027Suche in Google Scholar PubMed

[33] Guo Q., Wu Z., Zhang X., Sun L., Li C., Phenylboronate-diol crosslinked glycopolymeric nanocarriers for insulin delivery at physiological pH, Soft Matter, 2014, 10, 911-920.10.1039/c3sm52485jSuche in Google Scholar PubMed

[34] Cheng C., Zhang X., Wang Y., Sun L., Li C., Phenylboronic acid-containing block copolymers: Synthesis, self-assembly, and application for intracellular delivery of proteins, New J. Chem., 2012, 36, 1413-1421.10.1039/c2nj20997gSuche in Google Scholar

[35] Cheng C., Zhang X., Xiang J., Wang Y., Zheng C., Lu Z., Li C., Development of novel self-assembled poly(3-acrylamidophenylboronic acid)/poly(2-lactobionamidoethyl methacrylate) hybrid nanoparticles for improving nasal adsorption of insulin, Soft Matter, 2012, 8, 765-773.10.1039/C1SM06085FSuche in Google Scholar

[36] Wang Y., Zhang X., Han Y., Cheng C., Li C., pH- and glucose-sensitive glycopolymer nanoparticles based on phenylboronic acid for triggered release of insulin, Carbohydr. Polym., 2012, 89, 124-131.10.1016/j.carbpol.2012.02.060Suche in Google Scholar PubMed

[37] Guo H., Guo Q., Chu T., Zhang X., Wu Z., Yu D., Glucose-sensitive polyelectrolyte nanocapsules based on layer-by-layer technique for protein drug delivery, J. Mater. Sci. Mater. Med., 2014, 25, 121-129.10.1007/s10856-013-5055-6Suche in Google Scholar PubMed

[38] Guo Q., Zhang T., An J., Wu Z., Zhao Y., Dai X., Zhang X., Li C., Block versus random amphiphilic glycopolymer nanopaticles as glucose-responsive vehicles, Biomacromolecules, 2015, 16, 3345-3356.10.1021/acs.biomac.5b01020Suche in Google Scholar PubMed

[39] Hoare T., Pelton R., Charge-switching, amphoteric glucose-responsive microgels with physiological swelling activity, Biomacromolecules, 2008, 9, 733-740.10.1021/bm701203rSuche in Google Scholar PubMed

[40] Xing S., Guan Y., Zhang Y., Kinetics of glucose-induced swelling of P(NIPAM-AAPBA) microgels, Macromolecules, 2011, 44, 4479-4486.10.1021/ma200586wSuche in Google Scholar

[41] Zhang Y., Guan Y., Zhou S., Synthesis and volume phase transitions of glucose-sensitive microgels, Biomacromolecules, 2006, 7, 3196-3201.10.1021/bm060557sSuche in Google Scholar PubMed

[42] Wang D., Liu T., Yin J., Liu S., Stimuli-responsive fluorescent poly(N-isopropylacrylamide) microgels labeled with phenylboronic acid moieties as multifunctional ratiometric probes for glucose and temperatures, Macromolecules, 2011, 44, 2282-2290.10.1021/ma200053aSuche in Google Scholar

[43] Tang Z., Guan Y., Zhang Y., Contraction-type glucose-sensitive microgel functionalized with a 2-substituted phenylboronic acid ligand, Polym. Chem., 2014, 5, 1782-1790.10.1039/C3PY01190ASuche in Google Scholar

[44] Zhao L., Xiao C., Ding J., He P., Tang Z., Pang X., Zhuang X., Chen X., Facile one-pot synthesis of glucose-sensitive nanogel via thiol-ene click chemistry for self-regulated drug delivery, Acta Biomater., 2013, 9, 6535-6543.10.1016/j.actbio.2013.01.040Suche in Google Scholar PubMed

[45] Wu W., Chen S., Hu Y., Zhou S., A fluorescent responsive hybrid nanogel for closed-loop control of glucose, J. Diabetes Sci. Technol., 2012, 6, 892-901.10.1177/193229681200600421Suche in Google Scholar PubMed PubMed Central

[46] WuW., Shen J., Li Y., Zhu H., Banerjee P., Zhou S., Specific glucose-to-SPR signal transduction at physiological pH by molecularly imprinted responsive hybrid microgels, Biomaterials, 2012, 33, 7115-7125.10.1016/j.biomaterials.2012.06.031Suche in Google Scholar PubMed

[47] Ye T., Jiang X., Xu W., Zhou M., Hu Y., Wu W., Tailoring the glucose-responsive volume phase transition behaviour of Ag@poly(phenylboronic acid) hybrid microgels: From monotonous swelling to monotonous shrinking upon adding glucose at physiological pH, Polym. Chem., 2014, 5, 2352-2362.10.1039/c3py01564eSuche in Google Scholar

[48] Van Beek W.P., Smets L.A., Emmelot P., Increased sialic acid density in surface glycoprotein of transformed and malignant cells–a general phenomenon?, Cancer Res., 1973, 33, 2913-2922.Suche in Google Scholar

[49] Fuster M.M., Esko J.D., The sweet and sour of cancer: Glycans as novel therapeutic targets, Nat. Rev. Cancer, 2005, 5, 526-542.10.1038/nrc1649Suche in Google Scholar PubMed

[50] Otsuka H., Uchimura E., Koshino H., Okano T., Kataoka K., Anomalous binding profile of phenylboronic acid with N-acetylneuraminic acid (Neu5Ac) in aqueous solution with varying pH, J. Am. Chem. Soc., 2003, 125, 3493-3502.10.1021/ja021303rSuche in Google Scholar PubMed

[51] Djanashvili K., Frullano L., Peters J.A., Molecular recognition of sialic acid end groups by phenylboronates, Chem.-Eur. J., 2005, 11, 4010-4018.10.1002/chem.200401335Suche in Google Scholar PubMed

[52] Matsumoto A., Sato N., Kataoka K., Miyahara Y., Noninvasive sialic acid detection at cell membrane by using phenylboronic acid modified self-assembled monolayer gold electrode, J. Am. Chem. Soc., 2009, 131, 12022-12023.10.1021/ja902964mSuche in Google Scholar PubMed

[53] Han E., Ding L., Ju H., Highly sensitive fluorescent analysis of dynamic glycan expression on living cells using glyconanoparticles and functionalized quantum dots, Anal. Chem., 2011, 83, 7006-7012.10.1021/ac201488xSuche in Google Scholar PubMed

[54] Deng R., Yue J., Qu H., Liang L., Sun D., Zhang J., Liang C., Xu W., Xu S., Glucose-bridged silver nanoparticle assemblies for highly sensitive molecular recognition of sialic acid on cancer cells via surface-enhanced raman scattering spectroscopy, Talanta, 2018, 179, 200-206.10.1016/j.talanta.2017.11.006Suche in Google Scholar PubMed

[55] Deshayes S., Cabral H., Ishii T., Miura Y., Kobayashi S., Yamashita T., Matsumoto A., Miyahara Y., Nishiyama N., Kataoka K., Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes in solid tumors, J. Am. Chem. Soc., 2013, 135, 15501-15507.10.1021/ja406406hSuche in Google Scholar PubMed

[56] Aguirre-Chagala Y.E., Santos J.L., Huang Y., Herrera-Alonso M., Phenylboronic acid-installed polycarbonates for the pH-dependent release of diol-containing molecules, ACSMacro Lett., 2014, 3, 1249-1253.10.1021/mz500594mSuche in Google Scholar

[57] Zhang X., Zhang Z., Su X., Cai M., Zhuo R., Zhong Z., Phenylboronic acid-functionalized polymeric micelles with a HepG2 cell targetability, Biomaterials, 2013, 34, 10296-10304.10.1016/j.biomaterials.2013.09.042Suche in Google Scholar PubMed

[58] Liu H., Li Y., Sun K., Fan J., Zhang P., Meng J., Wang S., Jiang L., Dual-responsive surfaces modified with phenylboronic acid-containing polymer brush to reversibly capture and release cancer cells, J. Am. Chem. Soc., 2013, 135, 7603-7609.10.1021/ja401000mSuche in Google Scholar PubMed

[59] Matsumura Y.,Maeda H., A new concept for macromoleculartherapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Res., 1986, 46, 6387-6392.Suche in Google Scholar

[60] Yang Z., Sun N., Cheng R., Zhao C., Liu Z., Li X., Liu J., Tian Z., pH multistage responsive micellar system with charge-switch and PEG layer detachment for co-delivery of paclitaxel and curcumin to synergistically eliminate breast cancer stem cells, Biomaterials, 2017, 147, 53-67.10.1016/j.biomaterials.2017.09.013Suche in Google Scholar PubMed

[61] Gao W., Li S., Liu Z., Sun Y., Cao W., Tong L., Cui G., Tang B., Targeting and destroying tumor vasculature with a near-infrared laser-activated "nanobomb" for efficient tumor ablation, Biomaterials, 2017, 139, 1-11.10.1016/j.biomaterials.2017.05.037Suche in Google Scholar PubMed

[62] Liu A., Peng S., Soo J.C., Kuang M., Chen P., Duan H., Quantum dots with phenylboronic acid tags for specific labeling of sialic acids on living cells, Anal. Chem., 2011, 83, 1124-1130.10.1021/ac1028853Suche in Google Scholar PubMed

[63] Zhang X., Chen B., He M., Zhang Y., Peng L., Hu B., Boronic acid recognition based-gold nanoparticle-labeling strategy for the assay of sialic acid expression on cancer cell surface by inductively coupled plasma mass spectrometry, Analyst, 2016, 141, 1286-1293.10.1039/C5AN02402ASuche in Google Scholar PubMed

[64] Zhao D., Xu J.-Q., Yi X.-Q., Zhang Q., Cheng S.-X., Zhuo R.-X., Li F., pH-activated targeting drug delivery system based on the selective binding of phenylboronic acid, ACS Appl. Mater. Inter., 2016, 8, 14845-14854.10.1021/acsami.6b04737Suche in Google Scholar PubMed

[65] Lee J.-Y., Chung S.-J., Cho H.-J., Kim D.-D., Phenylboronic acid-decorated chondroitin sulfate A-based theranostic nanoparticles for enhanced tumor targeting and penetration, Adv. Funct.Mater., 2015, 25, 3705-3717.10.1002/adfm.201500680Suche in Google Scholar

[66] Jeong J.Y., Hong E.-H., Lee S.Y., Lee J.-Y., Song J.-H., Ko S.-H., Shim J.-S., Choe S., Kim D.-D., Ko H.-J., Cho H.-J., Boronic acid-tetheredamphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration, Acta Biomater., 2017, 53, 414-426.10.1016/j.actbio.2017.02.030Suche in Google Scholar PubMed

[67] Wang X., Tang H., Wang C., Zhang J., Wu W., Jiang X., Phenylboronic acid-mediated tumor targeting of chitosan nanoparticles, Theranostics, 2016, 6, 1378-1392.10.7150/thno.15156Suche in Google Scholar PubMed PubMed Central

[68] Ji M., Li P., Sheng N., Liu L., Pan H., Wang C., Cai L., Ma Y., Sialic acid-targeted nanovectorswith phenylboronic acid-grafted polyethylenimine robustly enhance siRNA-based cancer therapy, ACS Appl. Mater. Inter., 2016, 8, 9565-9576.10.1021/acsami.5b11866Suche in Google Scholar PubMed

[69] Kim J., Lee Y.M., Kim H., Park D., Kim J., Kim W.J., Phenylboronic acid-sugar grafted polymer architecture as a dual stimuli-responsive gene carrier for targeted anti-angiogenic tumor therapy, Biomaterials, 2016, 75, 102-111.10.1016/j.biomaterials.2015.10.022Suche in Google Scholar PubMed

[70] Zenkl G., Klimant I., Fluorescent acrylamide nanoparticles for boronic acid based sugar sensing - from probes to sensors, Microchim. Acta, 2009, 166, 123-131.10.1007/s00604-009-0172-0Suche in Google Scholar

[71] Wu W., Zhou T., Shen J., Zhou S., Optical detection of glucose by CdS quantum dots immobilized in smart microgels, Chem. Commun., 2009, 4390-4392.10.1039/b907348eSuche in Google Scholar PubMed

[72] Egawa Y., Seki T., Takahashi S., Anzai J.-i., Electrochemical and optical sugar sensors based on phenylboronic acid and its derivatives, Mater. Sci. Eng. C-Mater., 2011, 31, 1257-1264.10.1016/j.msec.2011.05.007Suche in Google Scholar

[73] Li J.,Wang Z., Li P., Zong N., Li F., A sensitive non-enzyme sensing platform for glucose based on boronic acid-diol binding, Sensors Actuat. B-Chem., 2012, 161, 832-837.10.1016/j.snb.2011.11.042Suche in Google Scholar

[74] Yetisen A.K., Montelongo Y., da Cruz Vasconcellos F., Martinez-Hurtado J.L., Neupane S., Butt H., Qasim M.M., Blyth J., Burling K., Carmody J.B., Evans M., Wilkinson T.D., Kubota L.T., Monteiro M.J., Lowe C.R., Reusable, robust, and accurate laser-generated photonic nanosensor, Nano Lett., 2014, 14, 3587-3593.10.1021/nl5012504Suche in Google Scholar PubMed

[75] Tram N., Magda J.J., Tathireddy P., Manipulation of the isoelectric point of polyampholytic smart hydrogels in order to increase the range and selectivity of continuous glucose sensors, Sensors Actuat. B-Chem., 2018, 255, 1057-1063.10.1016/j.snb.2017.08.022Suche in Google Scholar

[76] Zhou Y., Dong H., Liu L., Liu J., Xu M., A novel potentiometric sensor based on a poly(anilineboronic acid)/graphene modified electrode for probing sialic acid through boronic acid-diol recognition, Biosens. Bioelectron., 2014, 60, 231-236.10.1016/j.bios.2014.04.012Suche in Google Scholar PubMed

[77] Ang S.H., Thevarajah M., Alias Y., Khor S.M., Current aspects in hemoglobin A1c detection: A review, Clin. Chim. Acta, 2015, 439, 202-211.10.1016/j.cca.2014.10.019Suche in Google Scholar PubMed

[78] Wang X., Dong J., Ming H., Ai S., Sensing of glycoprotein via a biomimetic sensor based on molecularly imprinted polymers and graphene-Au nanoparticles, Analyst, 2013, 138, 1219-1225.10.1039/c2an36297jSuche in Google Scholar PubMed

[79] Amin R., Elfeky S.A., Fluorescent sensor for bacterial recognition, Spectrochim. Acta A, 2013, 108, 338-341.10.1016/j.saa.2013.02.041Suche in Google Scholar PubMed

[80] Dechtrirat D., Gajovic-Eichelmann N., Wojcik F., Hartmann L., Bier F.F., Scheller F.W., Electrochemical displacement sensor based on ferrocene boronic acid tracer and immobilized glycan for saccharide binding proteins and E. coli, Biosens. Bioelectron., 2014, 58, 1-8.10.1016/j.bios.2014.02.028Suche in Google Scholar PubMed

[81] Wang J., Gao J., Liu D., Han D., Wang Z., Phenylboronic acid functionalized gold nanoparticles for highly sensitive detection of staphylococcus aureus, Nanoscale, 2012, 4, 451-454.10.1039/C2NR11657JSuche in Google Scholar

[82] Khanal M., Vausselin T., Barras A., Bande O., Turcheniuk K., Benazza M., Zaitsev V., Teodorescu C.M., Boukherroub R., Siriwardena A., Dubuisson J., Szunerits S., Phenylboronic-acid-modified nanoparticles: Potential antiviral therapeutics, ACS Appl. Mater. Inter, 2013, 5, 12488-12498.10.1021/am403770qSuche in Google Scholar PubMed

[83] Huang L.-L., Jin Y.-J., Zhao D., Yu C., Hao J., Xie H.-Y., A fast and biocompatible living virus labeling method based on sialic acid-phenylboronic acid recognition system, Anal. Bioanal. Chem., 2014, 406, 2687-2693.10.1007/s00216-014-7651-9Suche in Google Scholar PubMed

[84] Jin Q., Lv L.-P., Liu G.-Y., Xu J.-P., Ji J., Phenylboronic acid as a sugar- and pH-responsive trigger to tune the multiple micellization of thermo-responsive block copolymer, Polymer, 2010, 51, 3068-3074.10.1016/j.polymer.2010.04.061Suche in Google Scholar

[85] Kim J., Lee J., Lee Y.M., Pramanick S., Im S., Kim W.J., Andrographolide-loaded polymerized phenylboronic acid nanoconstruct for stimuli-responsive chemotherapy, J. Control. Release, 2017, 259, 203-211.10.1016/j.jconrel.2016.10.029Suche in Google Scholar PubMed

[86] Prosperi-Porta G., Kedzior S., Muirhead B., Sheardown H., Phenylboronic-acid-based polymeric micelles for mucoadhesive anterior segment ocular drug delivery, Biomacromolecules, 2016, 17, 1449-1457.10.1021/acs.biomac.6b00054Suche in Google Scholar PubMed

[87] Ren J., Zhang Y., Zhang J., Gao H., Liu G., Ma R., An Y., Kong D., Shi L., pH/sugar dual responsive core-cross-linked PIC micelles for enhanced intracellular protein delivery, Biomacromolecules, 2013, 14, 3434-3443.10.1021/bm4007387Suche in Google Scholar PubMed

[88] Jia H.-z., Zhu J.-y., Wang X.-l., Cheng H., Chen G., Zhao Y.-f., Zeng X., Feng J., Zhang X.-z., Zhuo R.-x., A boronate-linked linear-hyperbranched polymeric nanovehicle for pH-dependent tumor-targeted drug delivery, Biomaterials, 2014, 35, 5240-5249.10.1016/j.biomaterials.2014.03.029Suche in Google Scholar PubMed

[89] Li S., Hu K., Cao W., Sun Y., Sheng W., Li F., Wu Y., Liang X.-J., pH-responsive biocompatible fluorescent polymer nanoparticles based on phenylboronic acid for intracellular imaging and drug delivery, Nanoscale, 2014, 6, 13701-13709.10.1039/C4NR04054FSuche in Google Scholar

[90] Aguirre-Chagala Y.E., Santos J.L., Aguilar-Castillo B.A., Herrera-Alonso M., Synthesis of copolymers from phenylboronic acid-installed cyclic carbonates, ACS Macro Lett., 2014, 3, 353-358.10.1021/mz500047pSuche in Google Scholar

[91] Yu F.,Wu H., Tang Y., Xu Y., Qian X., Zhu W., Temperature-sensitive copolymer-coated fluorescent mesoporous silica nanoparticles as a reactive oxygen species activated drug delivery system, Int. J. Pharm., 2017, 536, 11-20.10.1016/j.ijpharm.2017.11.025Suche in Google Scholar PubMed

Received: 2019-04-22
Accepted: 2019-08-22
Published Online: 2019-12-31

© 2019 T. Lan and Q. Guo, published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 Public License.

Artikel in diesem Heft

  1. Research Articles
  2. Investigation of rare earth upconversion fluorescent nanoparticles in biomedical field
  3. Carbon Nanotubes Coated Paper as Current Collectors for Secondary Li-ion Batteries
  4. Insight into the working wavelength of hotspot effects generated by popular nanostructures
  5. Novel Lead-free biocompatible piezoelectric Hydroxyapatite (HA) – BCZT (Ba0.85Ca0.15Zr0.1Ti0.9O3) nanocrystal composites for bone regeneration
  6. Effect of defects on the motion of carbon nanotube thermal actuator
  7. Dynamic mechanical behavior of nano-ZnO reinforced dental composite
  8. Fabrication of Ag Np-coated wetlace nonwoven fabric based on amino-terminated hyperbranched polymer
  9. Fractal analysis of pore structures in graphene oxide-carbon nanotube based cementitious pastes under different ultrasonication
  10. Effect of PVA fiber on durability of cementitious composite containing nano-SiO2
  11. Cr effects on the electrical contact properties of the Al2O3-Cu/15W composites
  12. Experimental evaluation of self-expandable metallic tracheobronchial stents
  13. Experimental study on the existence of nano-scale pores and the evolution of organic matter in organic-rich shale
  14. Mechanical characterizations of braided composite stents made of helical polyethylene terephthalate strips and NiTi wires
  15. Mechanical properties of boron nitride sheet with randomly distributed vacancy defects
  16. Fabrication, mechanical properties and failure mechanism of random and aligned nanofiber membrane with different parameters
  17. Micro- structure and rheological properties of graphene oxide rubber asphalt
  18. First-principles calculations of mechanical and thermodynamic properties of tungsten-based alloy
  19. Adsorption performance of hydrophobic/hydrophilic silica aerogel for low concentration organic pollutant in aqueous solution
  20. Preparation of spherical aminopropyl-functionalized MCM-41 and its application in removal of Pb(II) ion from aqueous solution
  21. Electrical conductivity anisotropy of copper matrix composites reinforced with SiC whiskers
  22. Miniature on-fiber extrinsic Fabry-Perot interferometric vibration sensors based on micro-cantilever beam
  23. Electric-field assisted growth and mechanical bactericidal performance of ZnO nanoarrays with gradient morphologies
  24. Flexural behavior and mechanical model of aluminum alloy mortise-and-tenon T-joints for electric vehicle
  25. Synthesis of nano zirconium oxide and its application in dentistry
  26. Surface modification of nano-sized carbon black for reinforcement of rubber
  27. Temperature-dependent negative Poisson’s ratio of monolayer graphene: Prediction from molecular dynamics simulations
  28. Finite element nonlinear transient modelling of carbon nanotubes reinforced fiber/polymer composite spherical shells with a cutout
  29. Preparation of low-permittivity K2O–B2O3–SiO2–Al2O3 composites without the addition of glass
  30. Large amplitude vibration of doubly curved FG-GRC laminated panels in thermal environments
  31. Enhanced flexural properties of aramid fiber/epoxy composites by graphene oxide
  32. Correlation between electrochemical performance degradation and catalyst structural parameters on polymer electrolyte membrane fuel cell
  33. Materials characterization of advanced fillers for composites engineering applications
  34. Humic acid assisted stabilization of dispersed single-walled carbon nanotubes in cementitious composites
  35. Test on axial compression performance of nano-silica concrete-filled angle steel reinforced GFRP tubular column
  36. Multi-scale modeling of the lamellar unit of arterial media
  37. The multiscale enhancement of mechanical properties of 3D MWK composites via poly(oxypropylene) diamines and GO nanoparticles
  38. Mechanical properties of circular nano-silica concrete filled stainless steel tube stub columns after being exposed to freezing and thawing
  39. Arc erosion behavior of TiB2/Cu composites with single-scale and dual-scale TiB2 particles
  40. Yb3+-containing chitosan hydrogels induce B-16 melanoma cell anoikis via a Fak-dependent pathway
  41. Template-free synthesis of Se-nanorods-rGO nanocomposite for application in supercapacitors
  42. Effect of graphene oxide on chloride penetration resistance of recycled concrete
  43. Bending resistance of PVA fiber reinforced cementitious composites containing nano-SiO2
  44. Review Articles
  45. Recent development of Supercapacitor Electrode Based on Carbon Materials
  46. Mechanical contribution of vascular smooth muscle cells in the tunica media of artery
  47. Applications of polymer-based nanoparticles in vaccine field
  48. Toxicity of metallic nanoparticles in the central nervous system
  49. Parameter control and concentration analysis of graphene colloids prepared by electric spark discharge method
  50. A critique on multi-jet electrospinning: State of the art and future outlook
  51. Electrospun cellulose acetate nanofibers and Au@AgNPs for antimicrobial activity - A mini review
  52. Recent progress in supercapacitors based on the advanced carbon electrodes
  53. Recent progress in shape memory polymer composites: methods, properties, applications and prospects
  54. In situ capabilities of Small Angle X-ray Scattering
  55. Review of nano-phase effects in high strength and conductivity copper alloys
  56. Progress and challenges in p-type oxide-based thin film transistors
  57. Advanced materials for flexible solar cell applications
  58. Phenylboronic acid-decorated polymeric nanomaterials for advanced bio-application
  59. The effect of nano-SiO2 on concrete properties: a review
  60. A brief review for fluorinated carbon: synthesis, properties and applications
  61. A review on the mechanical properties for thin film and block structure characterised by using nanoscratch test
  62. Cotton fibres functionalized with plasmonic nanoparticles to promote the destruction of harmful molecules: an overview
https://doi.org/10.1515/ntrev-2019-0049
Schlagwörter für diesen Artikel
Phenylboronic acid; Polymeric nanomaterials; Polyols; Drug delivery
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Investigation of rare earth upconversion fluorescent nanoparticles in biomedical field
  3. Carbon Nanotubes Coated Paper as Current Collectors for Secondary Li-ion Batteries
  4. Insight into the working wavelength of hotspot effects generated by popular nanostructures
  5. Novel Lead-free biocompatible piezoelectric Hydroxyapatite (HA) – BCZT (Ba0.85Ca0.15Zr0.1Ti0.9O3) nanocrystal composites for bone regeneration
  6. Effect of defects on the motion of carbon nanotube thermal actuator
  7. Dynamic mechanical behavior of nano-ZnO reinforced dental composite
  8. Fabrication of Ag Np-coated wetlace nonwoven fabric based on amino-terminated hyperbranched polymer
  9. Fractal analysis of pore structures in graphene oxide-carbon nanotube based cementitious pastes under different ultrasonication
  10. Effect of PVA fiber on durability of cementitious composite containing nano-SiO2
  11. Cr effects on the electrical contact properties of the Al2O3-Cu/15W composites
  12. Experimental evaluation of self-expandable metallic tracheobronchial stents
  13. Experimental study on the existence of nano-scale pores and the evolution of organic matter in organic-rich shale
  14. Mechanical characterizations of braided composite stents made of helical polyethylene terephthalate strips and NiTi wires
  15. Mechanical properties of boron nitride sheet with randomly distributed vacancy defects
  16. Fabrication, mechanical properties and failure mechanism of random and aligned nanofiber membrane with different parameters
  17. Micro- structure and rheological properties of graphene oxide rubber asphalt
  18. First-principles calculations of mechanical and thermodynamic properties of tungsten-based alloy
  19. Adsorption performance of hydrophobic/hydrophilic silica aerogel for low concentration organic pollutant in aqueous solution
  20. Preparation of spherical aminopropyl-functionalized MCM-41 and its application in removal of Pb(II) ion from aqueous solution
  21. Electrical conductivity anisotropy of copper matrix composites reinforced with SiC whiskers
  22. Miniature on-fiber extrinsic Fabry-Perot interferometric vibration sensors based on micro-cantilever beam
  23. Electric-field assisted growth and mechanical bactericidal performance of ZnO nanoarrays with gradient morphologies
  24. Flexural behavior and mechanical model of aluminum alloy mortise-and-tenon T-joints for electric vehicle
  25. Synthesis of nano zirconium oxide and its application in dentistry
  26. Surface modification of nano-sized carbon black for reinforcement of rubber
  27. Temperature-dependent negative Poisson’s ratio of monolayer graphene: Prediction from molecular dynamics simulations
  28. Finite element nonlinear transient modelling of carbon nanotubes reinforced fiber/polymer composite spherical shells with a cutout
  29. Preparation of low-permittivity K2O–B2O3–SiO2–Al2O3 composites without the addition of glass
  30. Large amplitude vibration of doubly curved FG-GRC laminated panels in thermal environments
  31. Enhanced flexural properties of aramid fiber/epoxy composites by graphene oxide
  32. Correlation between electrochemical performance degradation and catalyst structural parameters on polymer electrolyte membrane fuel cell
  33. Materials characterization of advanced fillers for composites engineering applications
  34. Humic acid assisted stabilization of dispersed single-walled carbon nanotubes in cementitious composites
  35. Test on axial compression performance of nano-silica concrete-filled angle steel reinforced GFRP tubular column
  36. Multi-scale modeling of the lamellar unit of arterial media
  37. The multiscale enhancement of mechanical properties of 3D MWK composites via poly(oxypropylene) diamines and GO nanoparticles
  38. Mechanical properties of circular nano-silica concrete filled stainless steel tube stub columns after being exposed to freezing and thawing
  39. Arc erosion behavior of TiB2/Cu composites with single-scale and dual-scale TiB2 particles
  40. Yb3+-containing chitosan hydrogels induce B-16 melanoma cell anoikis via a Fak-dependent pathway
  41. Template-free synthesis of Se-nanorods-rGO nanocomposite for application in supercapacitors
  42. Effect of graphene oxide on chloride penetration resistance of recycled concrete
  43. Bending resistance of PVA fiber reinforced cementitious composites containing nano-SiO2
  44. Review Articles
  45. Recent development of Supercapacitor Electrode Based on Carbon Materials
  46. Mechanical contribution of vascular smooth muscle cells in the tunica media of artery
  47. Applications of polymer-based nanoparticles in vaccine field
  48. Toxicity of metallic nanoparticles in the central nervous system
  49. Parameter control and concentration analysis of graphene colloids prepared by electric spark discharge method
  50. A critique on multi-jet electrospinning: State of the art and future outlook
  51. Electrospun cellulose acetate nanofibers and Au@AgNPs for antimicrobial activity - A mini review
  52. Recent progress in supercapacitors based on the advanced carbon electrodes
  53. Recent progress in shape memory polymer composites: methods, properties, applications and prospects
  54. In situ capabilities of Small Angle X-ray Scattering
  55. Review of nano-phase effects in high strength and conductivity copper alloys
  56. Progress and challenges in p-type oxide-based thin film transistors
  57. Advanced materials for flexible solar cell applications
  58. Phenylboronic acid-decorated polymeric nanomaterials for advanced bio-application
  59. The effect of nano-SiO2 on concrete properties: a review
  60. A brief review for fluorinated carbon: synthesis, properties and applications
  61. A review on the mechanical properties for thin film and block structure characterised by using nanoscratch test
  62. Cotton fibres functionalized with plasmonic nanoparticles to promote the destruction of harmful molecules: an overview
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 10.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/ntrev-2019-0049/html?lang=de
Button zum nach oben scrollen