Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation.

Gene-activated matrix (GAM)-based therapeutics for tissue regeneration are limited by efficacy, the lack of spatiotemporal control and availability of target cells, all of which impact negatively on their translation to the clinic. Here, an advanced ultrasound-responsive GAM is described containing target cells that facilitates matrix-assisted sonoporation (MAS) to induce osteogenic differentiation. Ultrasound-responsive GAMs consisting of fibrin/collagen hybrid-matrices containing microbubbles, bone morphogenetic protein BMP2/7 coexpression plasmids together with C2C12 cells were treated with ultrasound either in vitro or following parenteral intramuscular implantation in vivo. Using direct measurement for alkaline phosphatase activity, von Kossa staining and immunohistochemical analysis for osteocalcin expression, MAS-stimulated osteogenic differentiation was confirmed in the GAMs in vitro 7 days after treatment with ultrasound. At day 30 post-treatment with ultrasound, ectopic osteogenic differentiation was confirmed in vivo using X-ray microcomputed tomography and histological analysis. Osteogenic differentiation was indicated by the presence of ectopic bone structures in all animals treated with MAS. In addition, bone volumes in this group were statistically greater than those in the control groups. This novel approach of incorporating a MAS capability into GAMs could be exploited to facilitate ex vivo gene transfer with subsequent surgical implantation or alternatively provide a minimally invasive means of stimulating in situ transgene delivery for osteoinductive gene-based therapies. Copyright © 2017 John Wiley & Sons, Ltd.

A versatile, stimulus-responsive nanoparticle-based platform for use in both sonodynamic and photodynamic cancer therapy.

A PLGA-based multifunctional biodegradable nanoparticle platform co-harboring hematoporphyrin and indocyanine green has been developed. In vitro studies demonstrate ultrasound and light stimulated generation of cytotoxic reactive oxygen species. In vivo studies show that the ICG component facilitates nIR fluorescence imaging that demonstrates accumulation of IV- administered nanoparticles in tumours. In vivo studies also demonstrate ultrasound- and light-mediated inhibition of tumour growth in animals treated with the platform. Since the platform consists entirely of clinically-approved agents it could find use in sonodynamic- and photodynamic-based therapies for cancer. STATEMENT OF SIGNIFICANCE: We describe a biocompatible and biodegradable nanoparticle-based platform for use in sonodynamic and photodynamic therapeutic approaches for the treatment of cancer. The non-toxic nanoparticles produce cytotoxic reactive oxygen species when exposed to ultrasound and/or light at levels that have no impact on tissues. The system is unique in that it is accumulated by tumours within six hours and has the ability to release its sensitising capability while retaining its imaging capability within a therapeutic time frame. The former could enhance dispersion and sensitising capabilities in less permeable tumour tissues and the latter permits the design of therapeutic approaches that minimize collateral damage to normal tissues.

Pt-based electro-catalytic materials derived from biosorption processes and their exploitation in fuel cell technology.

Yeast-based biomass, immobilised in polyvinyl alcohol (PVA) cryogels, was used as a biosorbant material for the recovery of platinum (PtCl (6) (2-) ) from aqueous solutions. The resulting biomass-Pt matrices were then employed directly as an electro-catalytic anode in a fuel cell configuration to generate electrical energy from renewable sources such as glucose and ethanol. We suggest an integrated strategy incorporating the derivation of a high-value product from a bioremediative process with a view towards producing energy from renewable fuels such as glucose and ethanol.