Volume 11, Issue 22 - Special Issue: Novel Two-Dimensional Materials Based Bio-Nanophotonic

Phototherapy attracts increasing interest for broad bio-applications due to its noninvasive and highly selective nature. Owing to their good biocompatibility, unique optoelectronic properties and size/surface effects, carbon nanomaterials show great promise for phototherapy. Various carbon nanomaterials have been demonstrated as efficient phototherapy agents for a large variety of phototherapeutic applications, including cancer treatment, anti-bacteria, and Alzheimer’s disease. This review summarizes the recent progress of carbon nanomaterials for phototherapy. Current challenges and future perspectives are also discussed.

As a “star material”, 2D transition metal carbides and/or nitrides (MXenes) have tremendous potential applications in biosensor development and molecular imaging. MXenes have a lot of advantages due to their large specific surface, excellent electrical conductivity, adjustable band gap, and easy modification. MXenes that immobilized with DNA strands, proteins, enzymes, or other bioluminescent materials on the surface, have been used to measure small molecules with extraordinary sensitivity and remarkable limit of detection. This review provides an overview of most recent development in the synthesis, fundamental properties, biosensing, and molecular imaging applications of MXenes. We focused on molecular detection through MXene-based electrochemical properties their challenges and novel opportunities of MXenes in biological applications. This article will provide a guide for researchers who are interested in the application of MXenes biosensors.

Two-dimensional (2D) transition metal carbides and nitrides (MXenes) with fascinating physicochemical properties, ultrathin lamellar structure, high specific surface area, and excellent biocompatibility have been extensively explored in biomedical applications over the past decade. Photonic MXene nanomedicine and materdicine, as one of the most burgeoning emerging treatment modalities, are of great research interest owing to their photon utilization ability and high therapeutic efficiency. This review aims to summarize and discuss the very-recent advances in engineering 2D MXenes for photonic theranostic applications. We initially concentrate on the synthesis methods, surface modification, and functionalization with respect to MXenes. Furthermore, the photonic biological applications including photonic antibacteria, photonic bioimaging, photonic therapy, and photonic theranostics are highlighted in detail with the selected paradigms. Finally, the current challenges and future directions for 2D MXene biomaterials in regard to their photonic biomedicines are discussed in depth, aiming to drive the speed of their practical applications in clinic.

With the maturing techniques for advanced synthesis and engineering of two-dimensional (2D) materials, its nanocomposites, hybrid nanostructures, alloys, and heterostructures, researchers have been able to create materials with improved as well as novel functionalities. One of the major applications that have been taking advantage of these materials with unique properties is biomedical devices, which currently prefer to be decentralized and highly personalized with good precision. The unique properties of these materials, such as high surface to volume ratio, a large number of active sites, tunable bandgap, nonlinear optical properties, and high carrier mobility is a boon to ‘onics’ (photonics/electronics) and ‘omics’ (genomics/exposomics) technologies for developing personalized, low-cost, feasible, decentralized, and highly accurate medical devices. This review aims to unfold the developments in point-of-care technology, the application of ‘onics’ and ‘omics’ in point-of-care medicine, and the part of two-dimensional materials. We have discussed the prospects of photonic devices based on 2D materials in personalized medicine and briefly discussed electronic devices for the same.

Highly infectious viral diseases are a serious threat to mankind as they can spread rapidly among the community, possibly even leading to the loss of many lives. Early diagnosis of a viral disease not only increases the chance of quick recovery, but also helps prevent the spread of infections. There is thus an urgent need for accurate, ultrasensitive, rapid, and affordable diagnostic techniques to test large volumes of the population to track and thereby control the spread of viral diseases, as evidenced during the COVID-19 and other viral pandemics. This review paper critically and comprehensively reviews various emerging nanophotonic biosensor mechanisms and biosensor technologies for virus detection, with a particular focus on detection of the SARS-CoV-2 (COVID-19) virus. The photonic biosensing mechanisms and technologies that we have focused on include: (a) plasmonic field enhancement via localized surface plasmon resonances, (b) surface enhanced Raman scattering, (c) nano-Fourier transform infrared (nano-FTIR) near-field spectroscopy, (d) fiber Bragg gratings, and (e) microresonators (whispering gallery modes), with a particular emphasis on the emerging impact of nanomaterials and two-dimensional materials in these photonic sensing technologies. This review also discusses several quantitative issues related to optical sensing with these biosensing and transduction techniques, notably quantitative factors that affect the limit of detection (LoD), sensitivity, specificity, and response times of the above optical biosensing diagnostic technologies for virus detection. We also review and analyze future prospects of cost-effective, lab-on-a-chip virus sensing solutions that promise ultrahigh sensitivities, rapid detection speeds, and mass manufacturability.

As a key branch of the cross-discipline biophotonics, phototherapy, including photodynamic therapy (PDT), and photothermal therapy (PTT), is promising in biomedicine and visible light-driving PDT has been applied to clinical treatment. However, extensive applications of phototherapy are limited by the hypoxic microenvironment, laser penetration depth, and potential complexity for combined PDT/PTT. Thus, NIR-responsive oxygen self-supply nanocomposites functionalized with photosensitizers for achieving simultaneous in-depth PDT/PTT are urgently required. Herein, a multifunctional platform has been fabricated by co-immobilizing monodispersed ultrasmall Pd nanoclusters and a photosensitizer 5,10,15,20-Tetrakis (4-Aminophenyl)-21H,23H Porphyrin (Thp) on the surface of Ti 3 C 2 T x MXene nanosheets, generating the Pd-Thp-Ti 3 C 2 T x nanocomposite. Material characterization demonstrated that Pd nanoclusters and Thp were well-distributed on the MXene surface while MXene maintained its photothermal conversion efficiency and broad absorption. In this nanoplatform, irradiated by the single 808 nm laser, Pd selectively catalyzed the decomposition of H 2 O 2 to O 2 , and O 2 was continuously supplied to Thp for enhanced NIR-driving PDT. The in vivo fluorescence and photothermal imaging demonstrated the pronounced accumulation of nanocomposites in the tumor site. Both in vitro and in vivo results clearly demonstrated the nanocomposite had good biocompatibility, and that the synergistic PTT and enhanced PDT made apoptosis of the tumor cell achievable. This work not only proves this Pd-Thp-Ti 3 C 2 T x nanocomposite serves a promising solution for tumor hypoxia by inducing apoptosis of tumor cells with synergistic PTT and PDT, but also broadens the application of promising optical materials in biomedical field.

Photodynamic therapy (PDT) has lately been identified as a promising anticancer method and gained tremendous interest due to its controllability, non-invasive nature, and negligible side effects. Nevertheless, the development of PDT is hampered by two factors. One is the insufficient tissue penetration of phototherapy laser, resulting in restricted treatment sites. Another one is the substantial dependence of reactive oxygen species (ROS) formation on oxygen concentration. Therefore, a strategy to promote ROS generation by overcoming the hypoxia microenvironment is critical to cancer therapy. Electrolysis of water is known to be a rapid and relatively secure method for producing oxygen. Thus, in this study, electrotherapy was introduced to alleviate the tumor hypoxia by producing oxygen in situ , hence boosting the PDT efficacy, namely E-PDT. Black phosphorus (BP) based nanomaterials were selected as clearable photosensitizers with outstanding PDT performance. Experiments conducted both in vitro and in vivo indicated that E-PDT performed superior therapeutic effects with the in situ generation of oxygen by electrotherapy compared with other groups. This work suggests a promising strategy for phototherapeutic anticancer efficiency enhancement.

Photodynamic therapy (PDT) for hypoxic tumors has attracted wide attention owing to its noninvasiveness, easy maneuverability, and instantaneity. However, hypoxia in tumors and penetration depth of conventional ultraviolet light has greatly weakened its performance. To solve these problems, under NIR-II light irradiation, squaric acid nanoparticles (SQ NPs) with superior reactive oxygen, especially, hydroxyl radicals (•OH) production performance were first utilized for hypoxic tumor therapy. SQ NPs with intense light capture capability, intense NIR emission, and excellent photobleaching resistance show continuous •OH generation capabilities under NIR-II laser excitation. Through the superior PDT performance, the growth of hypoxic tumors was effectively inhibited, and the survival rate of mice was improved. This work highlights the application of NIR-II photoexcitation in deep tissue type I photodynamic therapy of hypoxic tumors, which will facilitate the development of hypoxic tumor PDT in deep depth.

NK cells-based cancer therapy combined with chemotherapeutic drugs for the treatment of tumors can enhance the immunosensitivity of NK cells, increase the expression of NK cell receptors, and eventually boost the killing effect of NK cells on cancer cells. Selenium (Se) with different chemical structures can be metabolized into selenoproteins to regulate tumor and immune cells’ fate and functions. Herein, we found that, functionalized Se nanoparticles (SeNPs) combining with metformin (met) could amply the immunotherapeutic effects of NK92 cells against osteosarcoma cancer. The results revealed that TW80-SeNPs combined with met had the optimum performance on NK92 cells for HepG2 cells, owing to the increased ROS in HepG2 cells and the augmented expression of cell surface receptor proteins ULBP-3/4, PD-L1, MICA, and NK92 cell surface receptor proteins PD-1 and FasL. Additionally, TW80-SeNPs were gradually metabolized into selenoproteins (Gpx4 and TR1) into human osteosarcoma MG63 cells to reinforce the anticancer effect of NK92 cells by regulating the redox balance in the tumor microenvironment. This study provides a therapeutic approach in treating cancer itself or diabetes coupled with cancer. Moreover, it provides a multidrug strategy to improve immune cell function in practical applications, especially for synergistic immunotherapy of osteosarcoma.

Topological insulators have shown great potential for future optoelectronic technology due to their extraordinary optical and electrical properties. Photodetectors, as one of the most widely used optoelectronic devices, are crucial for sensing, imaging, communication, and optical computing systems to convert optical signals to electrical signals. Here we experimentally show a novel combination of topological insulators (TIs) and transition metal chalcogenides (TMDs) based self-powered photodetectors with ultra-low dark current and high sensitivity. The photodetector formed by a MoS 2 /Sb 2 Te 3 heterogeneous junction exhibits a low dark current of 2.4 pA at zero bias and 1.2 nA at 1V. It shows a high photoresponsivity of >150 mA W −1 at zero bias and rectification of 3 times at an externally applied bias voltage of 1V. The excellent performance of the proposed photodetector with its innovative material combination of TMDs and TIs paves the way for the development of novel high-performance optoelectronic devices. The TIs/TMDs transfer used to form the heterojunction is simple to incorporate into on-chip waveguide systems, enabling future applications on highly integrated photonic circuits.

Fluorescence microscopy based on fluorochrome has been rapidly developed as the candidate for morphological identification of pathogenic fungi over recent years, offering superior rapidity and efficacy over traditional culture methods. However, the intrinsic quenching properties of fluorescein limit the clinical application of fluorescence imaging. Herein, we report a nano-strategy by converting a commercial fluorescein dye, fluorescent brightener-33 (FB-33), into carbon dots (FB-CDs) through a one-pot hydrothermal method. FB-CDs exhibit a chitin-targeting capacity allowing the selective recognition and ultrafast imaging of fungi within 30 s. The fluorescence quantum yield of FB-CDs is 51.6% which is 8.6-fold higher than that of commercial dye, FB-33. Moreover, FB-CDs also display superstable fluorescence signals under continuous intense light irradiation for 2 h and long-term storage for more than 2 months. The significantly improved photobleaching resistance meets the prolonged fluorescence observation and quantitative analysis of microbial samples. This work offers a novel nanoconversion strategy of commercial dyes for point-of-care testing of pathogenic organisms.

Intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. This study aims to develop a new drug carrier with hematoma-specific response and high property. pH-sensitive liposomes (PSL) were developed. Fingolimod with ammonia borane were encapsulated in the phospholipid vesicles to integrate two drugs for treating ICH more effectively. pH sensitive PSL-FTY720/AB was characterized for various physicochemical parameters such as shape, surface morphology, vesicle size, zeta-potential, in-vitro drug release in different pH environment, cellular toxicity, in-vivo and ex-vivo tissue accumulation. In vivo results further confirmed that drug-loading nanoparticles effectively protected against ICH-induced brain injury through synergistic effect of anti-inflammation and anti-oxidation. Collectively, the present study confirmed that PSL-FTY720/AB can be an effective, safe, and a novel alternative treatment approach in ICH.

Transition-metal-doped semiconductor nanocrystals have received significant attention because of their attractive features deeming them invaluable in various technological fields including optoelectronics, bio-photonics, and energy conversion, to name a few. Of particular, these interests are two-dimensional materials with useful optical and magnetic properties combined with their large surface areas opening up new applications in biotechnology. These applications range from multimodal optical and magnetic bioimaging and sensing to measuring the weak magnetic field due to brain waves using their magneto-optic properties stemming from the exchange interaction between the transition metal dopants and the carrier spins. These magnetic 2D materials could also significantly advance the field of spintronics. In this work, we report on a study of the magnetic and magneto-optic properties of colloidal two-dimensional (2D) copper-doped CdSe nanoplatelets (NPLs) that are synthesized using a high-temperature colloidal technique. We carried out optical and circularly polarized magneto-photoluminescence spectrometry to investigate the magnetism in our solution-processed nanostructures doped with copper ion impurities. At cryogenic temperatures, two excitonic features are observed for doped NPLs, which are more prominent compared to the undoped NPLs. Furthermore, the excitonic circular polarization (CP) is recorded as a function of the applied magnetic field ( B ) and temperature ( T ). The detailed analysis provides a picture of the magneto-optical behavior of the doped 2D NPLs in the presence of paramagnetic copper ions. This work paves the way for significant advances in bio/nanophotonics where tunable optical and magnetic properties of doped nanoplatelets can be leveraged to make more efficient, flexible, and low-cost devices.

Surface-enhanced spectroscopies, such as surface-enhanced Raman scattering (SERS), fluorescence (SEF), circular dichroism, etc., are powerful tools for investigating nano-entities with high sensitivities. Owing to the giant local electric field confined in a plasmonic nanogap, nanogap-enhanced spectroscopies could detect samples with ultralow concentrations, even down to the single-molecule level for SERS and SEF. This great ability to detect analytes with ultralow concentrations provides opportunities for early diagnosis and monitoring in modern biomedicine. However, local laser excitations would inevitably bring about unwanted disruptive background perturbations, local heating, and the consequent geometry reshaping and biological analyte damages. Remote spectroscopies avoiding direct laser exposure to the samples can be treated as remarkable solutions. Here, we combined the nanoparticle-on-mirror (NPoM) family with the philosophy of remote spectroscopy to construct so-called “NPoM pairs” structures. They consist of two identical NPoMs with matched resonances yet separate functions either as receiving or transmitting antennas. A figure of merit for evaluating the remote spectroscopies was put forward, which accounts for the efficiencies in three processes, i.e., receiving, transporting, and transmitting. In addition, we experimentally demonstrated the performances of these NPoM pairs by proof-of-principle applications on the remote SERS and SEF. The optical access of the spectral information in these NPoM pairs both locally and remotely manifests themselves as fundamental building blocks for remote spectroscopies.

Mesoporous carbon spheres (MCSs) are widely used in the field of pollutants adsorption, energy storage and various biomedicine applications such as targeted delivery vector, phototherapy sensitizers, bioimaging contrast agents, etc. Current synthetic strategies including soft templating and hard templating methods generally have the limits of using expensive surfactants or lack of control over the pore structures. Therefore, the complex and uncontrollable pore structures limit its further clinical application. Herein, we proposed a new synthetic strategy to control the uniformity of pore channel arrangement in MCSs which can modulate the photonic property and the corresponding light controlled drug release property in intelligent drug delivery. The as obtained MCSs with relative uniform pore channel arrangement and long pore channels are demonstrated to have the best NIR light-induced drug release performance. This work provides not only new synthetic method to modulate pore structure characteristics and biophotonic property of MCSs, but also uniform MCSs as novel delivery platforms with advanced controlled release performance.

Two-dimensional transition metal carbides and nitrides (MXenes) nanosheets with high photothermal conversion efficiency as well as photothermal stability can efficiently generate remarkable hyperthermia for photothermal therapy (PTT) of cancer. However, mono-MXenes cannot exhibit precise diagnosis and treatment to complete ablation of cancer cells in the PTT process. To overcome this dilemma, an “all-in-one” nanoplatform of titanium carbide (Ti 3 C 2 ) MXene-based composite nanosheets is developed for magnetic resonance imaging (MRI)-guided multi-modal hyperthermia and chemodynamic tumor ablation, which was achieved by bonding of manganese ion on the surface of Ti 3 C 2 , and then was the functionalized nanosheets was modified by biocompatible PEG (Mn-Ti 3 C 2 @PEG). Due to magnetic and Fenton-like catalytic properties of Mn components, Mn-Ti 3 C 2 @PEG not only acted as the contrast agents for T 1 -weighted MRI (relaxivity value of 1.05 mM −1  s −1 ), but also converted cellular H 2 O 2 into highly toxic hydroxyl radicals (·OH) mediated chemodynamic therapy (CDT). Moreover, Furthermore, Mn-Ti 3 C 2 @PEG can efficiently suppressed tumor-growth by PTT, due to the high photothermal conversion capability and photothermal stability. As a proof-of-concept model, the as-designed Mn-Ti 3 C 2 @PEG nanoplatform shows simultaneous MRI and dual-modal treatment for effective suppression of tumor with minimized side effects both in vitro and in vivo , indicating the great potential for clinical cancer theranostics.

Nanodynamic therapy (NDT) based on reactive oxygen species (ROS) production has been envisioned as an effective cancer treatment. However, the efficacy is limited by the hypoxia, insufficient hydrogen peroxide conversion, and high glutathione (GSH) levels in the tumor microenvironment (TME). To solve these issues, we proposed and designed a biocompatible, oxygen resistant Cu-modified Ti 3 C 2 nanocomposite (Ti 3 C 2 -Cu-PEG), which can efficiently deplete the endogenous GSH in tumor cells, smartly respond to NIR-II light irradiation with in-depth tissue penetration to achieve photothermally enhanced tumor photodynamic therapy (PDT) and catalytic therapy. Specifically, Ti 3 C 2 -Cu-PEG reacted with oxygen to produce singlet oxygen ( 1 O 2 ) under NIR-II irradiation, and catalyzed the highly expressed H 2 O 2 in the tumor microenvironment to generate ·OH. In addition, Ti 3 C 2 -Cu-PEG significantly decreased intracellular GSH, reduced the chances of reaction between ROS and GSH, and thus promoting ROS effect. Moreover, the intrinsically high photothermal conversion efficiency of Ti 3 C 2 -Cu-PEG further promotes the NDT process. In vitro and in vivo experiments, the Ti 3 C 2 -Cu-PEG nanosystem showed excellent antitumor effect in 4T1 tumor-bearing mice by amplifying oxidative stress under NIR-II stimulation. This work highlights an easily synergistic nanosystem with remodeling TME and combined photothermal therapy to enhance the therapeutic effect of NDT in tumor therapy.