Bioinspired soft nanovesicles for site-selective cancer imaging and targeted therapies.

Cell-to-cell communication within the heterogeneous solid tumor environment plays a significant role in the uncontrolled metastasis of cancer. To inhibit the metastasis and growth of cancer cells, various chemically designed and biologically derived nanosized biomaterials have been applied for targeted cancer therapeutics applications. Over the years, bioinspired soft nanovesicles have gained tremendous attention for targeted cancer therapeutics due to their easy binding with tumor microenvironment, natural targeting ability, bio-responsive nature, better biocompatibility, high cargo capacity for multiple therapeutics agents, and long circulation time. These cell-derived nanovesicles guard their loaded cargo molecules from immune clearance and make them site-selective to cancer cells due to their natural binding and delivery abilities. Furthermore, bioinspired soft nanovesicles prevent cell-to-cell communication and secretion of cancer cell markers by delivering the therapeutics agents predominantly. Cell-derived vesicles, namely, exosomes, extracellular vesicles, and so forth have been recognized as versatile carriers for therapeutic biomolecules. However, low product yield, poor reproducibility, and uncontrolled particle size distribution have remained as major challenges of these soft nanovesicles. Furthermore, the surface biomarkers and molecular contents of these vesicles change with respect to the stage of disease and types. Here in this review, we have discussed numerous examples of bioinspired soft vesicles for targeted imaging and cancer therapeutic applications with their advantages and limitations. Importance of bioengineered soft nanovesicles for localized therapies with their clinical relevance has also been addressed in this article. Overall, cell-derived nanovesicles could be considered as clinically relevant platforms for cancer therapeutics. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanowall Textured Hydrophobic Surfaces and Liquid Droplet Impact.

Water droplet impact on nanowires/nanowalls' textured hydrophobic silicon surfaces was examined by assessing the influence of texture on the droplet impact dynamics. Silicon wafer surfaces were treated, resulting in closely packed nanowire/nanowall textures with an average spacing and height of 130 nm and 10.45 µm, respectively. The top surfaces of the nanowires/nanowalls were hydrophobized through the deposition of functionalized silica nanoparticles, resulting in a droplet contact angle of 158° ± 2° with a hysteresis of 4° ± 1°. A high-speed camera was utilized to monitor the impacting droplets on hydrophobized nanowires/nanowalls' textured surfaces. The nanowires/nanowalls texturing of the surface enhances the pinning of the droplet on the impacted surface and lowers the droplet spreading. The maximum spreading diameter of the impacting droplet on the hydrophobized nanowires/nanowalls surfaces becomes smaller than that of the hydrophobized as-received silicon, hydrophobized graphite, micro-grooved, and nano-springs surfaces. Penetration of the impacted droplet fluid into the nanowall-cell structures increases trapped air pressure in the cells, acting as an air cushion at the interface of the droplet fluid and nanowalls' top surface. This lowers the droplet pinning and reduces the work of droplet volume deformation while enhancing the droplet rebound height.

Geometric Modulation of Local CO Flux in Ag@Cu2 O Nanoreactors for Steering the CO2 RR Pathway toward High-Efficacy Methane Production.

The electroreduction of carbon dioxide (CO2 RR) to CH4 stands as one of the promising paths for resourceful CO2 utilization in meeting the imminent "carbon-neutral" goal of the near future. Yet, limited success has been witnessed in the development of high-efficiency catalysts imparting satisfactory methane selectivity at a commercially viable current density. Herein, a unique category of CO2 RR catalysts is fabricated with the yolk-shell nanocell structure, comprising an Ag core and a Cu2 O shell that resembles the tandem nanoreactor. By fixing the Ag core and tuning the Cu2 O envelope size, the CO flux arriving at the oxide-derived Cu shell can be regulated, which further modulates the *CO coverage and *H adsorption at the Cu surface, consequently steering the CO2 RR pathway. Density functional theory simulations show that lower CO coverage favors methane formation via stabilizing the intermediate *CHO. As a result, the best catalyst in the flow cell shows a high CH4 Faraday efficiency of 74 ± 2% and partial current density of 178 ± 5 mA cm- 2 at -1.2 VRHE , ranking above the state-of-the-art catalysts reported today for methane production. These findings mark the significance of precision synthesis in tailoring the catalyst geometry for achieving desired CO2 RR performance.

RET Kinase-Regulated MicroRNA-153-3p Improves Therapeutic Efficacy in Medullary Thyroid Carcinoma.

Background: Medullary thyroid carcinoma (MTC) presents a disproportionate number of thyroid cancer deaths due to limited treatment options beyond surgery. Gain-of-function mutations of the human REarranged during Transfection (RET) proto-oncogene have been well-established as the key driver of MTC tumorigenesis. RET has been targeted by tyrosine kinase inhibitors (TKIs), such as cabozantinib and vandetanib. However, clinical results have been disappointing, with regular dose reductions and inevitable progression. This study aimed to identify RET-regulated microRNAs (miRNAs) and explore their potential as novel therapeutic targets. Methods: Small RNA sequencing was performed in MTC TT cells before and after RET inhibition to identify RET-regulated miRNAs of significance. In vitro gain-of-function studies were performed to investigate cellular and molecular effects of potential miRNAs on cell phenotypes. Systemic delivery of miRNA in MTC xenografts using EDV™ nanocells, targeted to epidermal growth factor receptor on tumor cells, was employed to assess the therapeutic potential and possible modulation of TKI responses. Results: The study demonstrates the tumor suppressive role of a specific RET-regulated miRNA, microRNA-153-3p (miR-153-3p), in MTC. Targeted intravenous delivery of miR-153-3p impeded the tumor growth in MTC xenografts. Furthermore, combined treatment with miR-153-3p plus cabozantinib caused greater growth inhibition and appeared to reverse cabozantinib resistance. Mechanistically, miR-153-3p targets ribosomal protein S6 kinase B1 (RPS6KB1) of mTOR signaling and reduced downstream phosphorylation of Bcl-2 associated death promoter. Conclusion: This study provides evidence to establish systemic miRNA replacement plus TKIs as a novel therapeutic for patients with metastatic, progressive MTC.

Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals.

Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice.