What’s up in nanomedicine?

Publications digest

Nanomaterial bio-screening platform for neurological applications

Neural cells are classified into glia cells and neurons. The neurons transmit electrical information, whereas the glia cells are the supporting cells and exceed the neurons by about 10-fold [1–4]. Jenkins and coworkers [5] found that magnetic nanoparticles were uptaken/handled differently among different glia cells. The microglia cells (immune components) were capable of an voracious and rapid uptake of the particles with extensive degradation. A significantly lower but stable particle accumulation was found in the other glial subtypes. Therefore, the microglial cells may function as a barrier to the uptake of particles where the neural cell populations are mixed as found in the intact nervous system. Until now, the latter was concluded from post-mortem observations only [6].

Glia cells are responsible for the clearance of nanomaterials [7] in the central nervous system, according to a study of Maysinger et al. [8] even for ∼99.5% and are therefore important when investigating new nanomaterials. They also emphasized that the interactions of biomolecules with the materials at nanoscale is of extreme importance. The biomolecules form a layer around the material (also called the protein corona [9–11]) thus becoming in direct contact with the cell and influencing the provided results of an investigation.

High throughput screening of new nanomaterials is still difficult as a result of the lack of accessible neural models [12]. In addition, current available biological models are limited due to, e.g., ethical and technical issues with laboratory animals, the limitations in the control of cellular stoichiometries and/or poor reproducibility. Jenkins et al. [13] developed a novel multi-glial cell-screening model suitable for the investigation of nanomaterials. The capabilities of the novel model were evaluated by investigating well-characterized magnetic particles and examining the hypothesis of the existence of a microglial barrier. The important features of the model are:

(1) The development of a standardized culture medium that can be used for all cell types. This gliosupportive medium ensures that the protein coronas of the magnetic particles are similar, which enables a real comparison of the particle uptake among different neural celltypes. The influences of different culture media including the developed gliosupportive medium were investigated by zeta potential measurements, dynamic light scattering and Fourier transform infrared spectroscopy (FTIR) analysis. Differences in the global secondary structure of the proteins of the corona were observed by FTIR, which emphasize the importance of a standardized medium. (2) The use of different cell-types that originate from a single source ensures identical treatment conditions for all cells and identical age and anatomical origin in an investigation. Differences in, e.g., culturing conditions or age may lead to differences in nanoparticle uptake. (3) A highly reproducible cellular stoichiometry was provided that enables reliable intercellular comparisons. (4) The model is compatible with other analytical and microscopic techniques. (5) Nanomaterials can be delivered easily.

With this novel approach, Jenkins and coworkers confirmed for the first time the existence of a competitive microglial barrier in real time and in addition, they demonstrated the influence of culture media on the particle coronas. This work is an example of excellent multidisciplinary work that enables the acceleration of novel (nano)materials for neuroregenerative application and in addition contributing to the limitation of live animal experiments.

PEDOT nanocomposites mediated sterilization

About one-third of global mortalities are caused by bacterial infection. Medical treatment with antibiotics is possible, however, the growing amount of resistant species is alarming. Reliable sterilization methods that have few side effects are urgently required. The field of phototherapeutics includes photothermal therapy (PTT) and photodynamic therapy (PDT).

PTT is a controllable, minimally-invasive and highly efficient method for sterilization that is based on the conversion of light energy into heat energy. Nanomaterials used for this include metal-based materials (e.g., Au [14, 15], Ag [16]), carbon based [17, 18] and semiconductor nanoparticles [19–22]. Polymeric nanoparticles are successfully used in vitro and in vivo for the photothermal treatment of cancer (e.g., [23, 24]). Interestingly, all of the developed conjugated polymeric nanoparticles absorb light in the near infrared region ranging from 700 to 950 nm, whereas the region from 1000 to 1250 nm received less attention. The latter has advantages in the penetration depth and the spatial scattering effect [25–27].

PDT comprises the use of harmless light and the use of non-toxic photosensitizers to produce cytotoxic free radicals. For in-depth treatment, photosensitizers with absorption wavelengths in the near-infrared regions are required. An FDA (Food and Drug Administration) approved example of near infrared photodynamic agent is indocyanine green (ICG).

PTT in combination with PDT has already been used to treat superficial cancers [26] but not for the treatment of bacterial infections. Li and coworkers [28] developed a novel agent that might be used in combination with PTT and PDT for the inactivation of pathogenic bacteria. The photothermal coupling agent poly(3,4-ethylenedioxythiophene) (PEDOT) was used since this material has a broad absorbance ranging from 700 to 1250 nm, suitable size ∼17 nm and a conversion efficiency of ∼71%. PEDOT nanoparticles (PEDOTs) were generated by using a hydrothermal method (environmental friendly). Then the photodynamic agent ICG was electrostatically coupled to the surface of the PEDOTs. Polyethylene glycol (PEG) and gluteraldehyde (GTA) were used to generate bacteria targeting properties. The nanoparticles were characterized using powder X-ray diffraction, FTIR spectrometer and a transmission electron microscope. The toxicity of the PEDOTs-ICG-PEG-GTA particles was investigated on Escherichia coli, Staphylococcus aureus, HeLa and U87MG cells by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method (assessment of cell viability as a function of the redox potential). Li and colleagues concluded that the particles have low toxicity and have a high biocompatibility. The photodynamic properties were investigated by detecting the reactive oxygen species generated by ICG after irradiation with an 808 nm laser (1.5 W) and by using the singlet oxygen sensor green reagent. From this it was concluded that the reactive oxygen production is considerably high. The photothermal properties were investigated by using a 1064 nm laser (1.5 W). Within 330 s, the temperature increases from 25.5°C to 76.6°C. Irradiation for 60 min showed the excellent photostability of the PEDOTs-ICG-PEG-GTA particles. The dual-modal sterilization of the PEDOTs-ICG-PEG-GTA particles were studied on various groups of E. coli and S. aureus: PTT + PDT (PEDOTs-ICG-PEG-GTA particles + 808, 1064 nm irradiation), PTT only (PEDOTs + 1064 nm irradiation), PDT only (ICG +808 nm), control group (PEDOTs-ICG-PEG-GTA particles 808 nm, 1064 nm) and an untreated group. From the experiments the scientists concluded that the developed dual sterilization method has a bacteria killing efficacy of ∼99%. With this, they open the door to a new generation of treatments of bacterial infections.

Bacteriophages and nanomedicine

Finally, a note to emphasize the possibilities that genetic engineering of M13 bacteriophages may offer for our field by pointing to the recent review of Chung and coworkers [29]. In this review, the authors introduce how chemoselective phage functionalization can be designed and how this might be applied in combination with the use of genetic engineering by presenting this for various recently reported medical applications.

Upcoming events

• The European Foundation for Clinical Nanomedicine CLINAM and collaborators organize the 8th European Summit for Clinical Nanomedicine and Targeted Medicine in Basel (Switzerland) from 28th June to 1st July. The purpose of this conference is to bring together researchers, practitioners, industry, ventures, political decision makers and is the place to be to present and discuss your work with the experts from the multidisciplinary field of nanomedicine and targeted medicine.

  The three medical focus fields for this year are: infection and inflammation, cancer and diabetes with debates dedicated to topics such as: personalized medicine, ethical and societal implications, novel materials, technologies and devices, antibodies vs. nanoparticle delivery, nanomedical imaging, tools for translational research and more. For more information about the conference and the invited speakers, see www.clinam.org.

• The Nanotech France 2015 will be held from June 15th to 17th (Paris–France) and covers all frontier topics in nanotechnology. This multidisciplinary conference is interesting for scientists, technology developers, practitioners and policy makers to exchange knowledge and information. Conference topics include advanced nanomaterials, nanoscale electronics, nanotech in life sciences and medicine and nanotechnology safety. An international exhibition and various short courses will be organized in parallel to the conference. For more information, see http://www.setcor.org/conferences/Nanotech-France-2015.

• The NN15 Nanotechnology Conference7–10 July 2015, to be held at Thessaloniki (Greece) is a world class event with a focus on the latest developments in nanosciences and nanotechnologies and market-related trends. This multidisciplinary conference is the place to be for experts in the research and application field, industry, and for students and practitioners to startup collaboration, to discuss their work and to exchange educational concepts. The conference also includes five workshops: (1) nanoelectronics; photonics; phononics; plasmonics; energy, (2) nanomaterials, nanofabrications, nanoengeneering and nanoconstruction, (3) nanomedicine, (4) bioelectronics and (5) graphene and related materials.

  For more information about the conference and the workshop, see: http://nnconf.physics.auth.gr.

Finally, I hope to meet you at the CLINAM summit from June 28 until July 1 at the Swiss Trade Fair congress Center (www.clinam.org).