Efficacy versus Toxicity - The Ying and Yang in Translating Nanomedicines

Nanomedicine, as a relatively new offshoot of nanotechnology, has presented vast opportunities in biomedical research for developing novel strategies to treat diseases. In the past decade, there has been a significant increase in in vitro and preclinical studies addressing the benefits of nanomedicines. In this commentary, we focus specifically on the efficacy- and toxicity-related translational challenges of nanocarrier-mediated systems, and briefly discuss possible strategies for addressing such issues at in vitro and preclinical stages. We address questions related specifically to the balance between toxicity and efficacy, a balance that is expected to be substantially different for nanomedicines compared to that for a free drug. Using case studies, we propose a ratiometric assessment tool to quantify the overall benefit of nanomedicine as compared to free drugs in terms of efficacy and toxicity. The overall goal of this commentary is to emphasize the strategies that promote the translation of nanomedicines, especially by learning lessons from previous translational failures of other drugs and devices, and to apply these lessons to critically assess data at the basic stages of nanomedicinal research

Surface Chemical Analysis of Solid-Electrolyte Interphase Layer on Germanium Thin Films and the Effect of Vinylene Carbonate Electrolyte Additive

Germanium thin-film anodes for Li-ion battery applications are the focus of the present work. As part of this chapter, we shall briefly review the use of germanium thin films in Li-ion batteries, and subsequently, new results pertaining to the effect of vinylene carbonate (VC) as electrolyte additive on the electrochemical performance are presented. We have used cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy to investigate the performance. Thin-film electrode performance with 0 wt. %, 5 wt. %, and 10 wt.% VC as electrolyte additive was compared to understand the role of additive’s concentration. The cell with 5 wt.% VC as electrolyte additive exhibited best performance with high specific capacity of 975 mAh/g, with a retention of 94 and 99% Coulombic efficiency at the end of 100 cycles. Ex situ surface chemical analysis of the solid-electrolyte interphase (SEI) layer has been studied in detail using X-ray photoelectron spectroscopy and correlated with the electrochemical performance

Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging

Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters (Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ~5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f7/2˜83.97 eV and Au 4f5/2~87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ~1 nm and protein cluster aggregates of size ~8 nm. Photoluminescence studies show bright fluorescence with peak maximum at ~674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 µg ml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer

Effect of TiO₂ nanotube length and lateral tubular spacing on photovoltaic properties of back illuminated dye sensitized solar cell

The main objective of this study is to show the effect of TiO2 nanotube length, diameter and intertubular lateral spacings on the performance of back illuminated Dye Sensitized Solar Cells (DSSCs). The present study shows that processing short TiO2 nanotubes with good lateral spacings could significantly improve the performance of back illuminated DSSCs. Vertically aligned, uniform sized diameter TiO2 nanotube arrays of different tube lengths have been fabricated on Ti plates by a controlled anodization technique at different times of 24, 36, 48 and 72 h using ethylene glycol and ammonium fluoride as an electrolyte medium. Scanning Electron Microscopy (SEM) showed formation of nanotube arrays spread uniformly over a large area. X-ray Diffraction (XRD) of TiO2 nanotube layer revealed the presence of crystalline anatase phases. By employing the TiO2 nanotube array anodized at 24 h showing a diameter ∼80 nm and length ∼1•5 μm as the photo-anode for back illuminated DSSCs, a full-sun conversion efficiency (η) of 3•5% was achieved, the highest value reported for this length of nanotubes

Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration

Recently, scaffolds for tissue regeneration purposes have been observed to utilize nanoscale features in an effort to reap the cellular benefits of scaffold features resembling extracellular matrix (ECM) components. However, one complication surrounding electrospun nanofibers is limited cellular infiltration. One method to ameliorate this negative effect is by incorporating nanofibers into microfibrous scaffolds. This study shows that it is feasible to fabricate electrospun scaffolds containing two differently scaled fibers interspersed evenly throughout the entire construct as well as scaffolds containing fibers composed of two discrete materials, specifically fibrin and poly(?-caprolactone). In order to accomplish this, multiscale fibrous scaffolds of different compositions were generated using a dual extrusion electrospinning setup with a rotating mandrel. These scaffolds were then characterized for fiber diameter, porosity and pore size and seeded with human mesenchymal stem cells to assess the influence of scaffold architecture and composition on cellular responses as determined by cellularity, histology and glycosaminoglycan (GAG) content. Analysis revealed that nanofibers within a microfiber mesh function to maintain scaffold cellularity under serum-free conditions as well as aid the deposition of GAGs. This supports the hypothesis that scaffolds with constituents more closely resembling native ECM components may be beneficial for cartilage regeneration

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01268-1

Long-Range π-Conjugation in Phenothiazine-containing Donor-Acceptor Dyes for Application in Dye-Sensitized Solar Cells

Four organic donor–π-bridge–acceptor dyes containing phenothiazine as a spacer and cyanoacrylic acid as an acceptor were synthesized and tested as sensitizers in dye-sensitized solar cells (DSCs). The influence of iodide- and cobalt-based redox electrolytes on the photovoltaic device performance was investigated. In these new dyes, systematic π-conjugation was extended by inserting one or two phenothiazine moieties and investigated within the context of the resulting photoinduced charge-transfer properties. A detailed investigation, including transient absorption spectroscopy and quantum chemical methods, provided important information on the role of extended π-conjugation on the photophysical properties and photovoltaic device performance. Overall, the results showed that the extension of π-conjugation by one phenothiazine unit resulted in the best device performance owing to reduced recombination rates, whereas extension by two phenothiazine units reduced dye adsorption on TiO2 probably owing to the increase in molecular size. The performance of the dyes in DSCs was found to be a complex interaction between dye structure and size

Chitin Scaffolds in Tissue Engineering

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine

Biomedical Applications of Polymeric Nanofibers

XII, 288 p.online resource

High-Performance Zr-Doped P3-Type Na_0.67Ni_0.33Mn_0.67O₂ Cathode for Na-Ion Battery Applications

Sodium-ion battery (SIB) technology started to bloom along with lithium-ion batteries (LIBs) as a supportive energy source to alleviate the cost of lithium sources for the development of energy storage devices and electric vehicles. Layered cathode materials are considered potential candidates to produce high-energy-density batteries. Among the layered cathode materials, P3-type cathodes are the least investigated in spite of their capacities, which are comparable to those of P2-type cathodes. P3-type cathodes show high polarization, leading to a poor cycle life, which impedes their extensive use in practical applications. In this work, we report on zirconium doping as an effective strategy to improve cycling stability and reduce voltage fading, another serious issue of layered cathode materials. It is found that an optimum composition of the P3-type cathode with Zr doping at the Mn site, leading to a composition of Na0.67Ni0.33Mn0.64Zr0.033O2, shows good electrochemical performance in terms of retention (89% after 100 cycles) when compared to Na0.67Ni0.33Mn0.60Zr0.067O2 (85% after 100 cycles) and an undoped sample (83% after 100 cycles). Also, remarkable performance is delivered by the Na0.67Ni0.33Mn0.64Zr0.033O2 sample, with a retention rate of 72% after 450 cycles. This result is also supported by an analysis of the amount of polarization for undoped and doped samples, which found that doping helps in improving the diffusion of ions, and the least polarization is obtained for the Na0.67Ni0.33Mn0.64Zr0.033O2 sample