Laser-Assisted Scalable Pore Fabrication in Graphene Membranes for Blue-Energy Generation.

The osmotic energy from a salinity gradient (i. e. blue energy) is identified as a promising non-intermittent renewable energy source for a sustainable technology. However, this membrane-based technology is facing major limitations for large-scale viability, primarily due to the poor membrane performance. An atomically thin 2D nanoporous material with high surface charge density resolves the bottleneck and leads to a new class of membrane material the salinity gradient energy. Although 2D nanoporous membranes show extremely high performance in terms of energy generation through the single pore, the fabrication and technical challenges such as ion concentration polarization make the nanoporous membrane a non-viable solution. On the other hand, the mesoporous and micro porous structures in the 2D membrane result in improved energy generation with very low fabrication complexity. In the present work, we report femtosecond (fs) laser-assisted scalable fabrication of µm to mm size pores on Graphene membrane for blue energy generation for the first time. A remarkable osmotic power in the order of µW has been achieved using mm size pores, which is about six orders of magnitudes higher compared to nanoporous membranes, which is mainly due to the diffusion-osmosis driven large ionic flux. Our work paves the way towards fs laser-assisted scalable pore creation in the 2D membrane for large-scale osmotic power generation.

Galactoxyloglucan-doxorubicin nanoparticles exerts superior cytotoxic effects on cancer cells-A mechanistic and in silico approach.

Galactoxyloglucan (PST001), isolated from seed kernel of Tamarindus indica is a non-toxic immunostimlatory agent with selective cytotoxicity on cancer cells. Toxicity associated with the chemotherapeutic drug doxorubicin (Dox) is the major barrier in its clinical application. Stable, spherically shaped PST-Dox nanoparticles with an average size of 10nm were prepared via ionic gelation of Dox with PST001 which displayed a pH dependent cumulative Dox release kinetics. PST-Dox nanoparticles demonstrated cancer-specific enhanced cytotoxic effects than PST001 and Dox in cancer cells by enhanced cellular uptake of Dox through the induction of apoptosis, sparing normal cells and RBCs. Elucidation of molecular mechanism by whole genome microarray revealed down-regulation of tyrosine kinase oncogenic pathways as PST-Dox mode of action. An in silico model of PST-Dox was developed and computed the activity against topoisomerase IIß, human Abl kinase and protein tyrosine kinases. Computational studies further affirmed the findings of genomic and proteomic investigations with an increased interaction energy between PST-Dox complexes with target system than with Dox and PST001 alone. The important findings and profoundly restrained methodologies highlighted in the current study will accelerate the therapeutic potential of this nanoparticle formulation for substantial clinical studies and testing in several cancers. To conclude, PST-Dox nanoparticles represent a superior drug delivery nanosystem for the effective treatment of cancer even though detailed investigations are warranted.

AS1411 aptamer and folic acid functionalized pH-responsive ATRP fabricated pPEGMA-PCL-pPEGMA polymeric nanoparticles for targeted drug delivery in cancer therapy.

Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ∼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (∼70%) compared to pH 7.4 (∼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.