Potentiating the Anticancer Properties of Bisphosphonates by Nanocomplexation with the Cationic Amphipathic Peptide, RALA

Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs possess anticancer potential, but exploitation of these antiproliferative properties is limited by their toxicities. We previously reported the utility of a cationic amphipathic fusogenic peptide, RALA, to traffic anionic nucleic acids into various cell types in the form of cationic nanoparticles. We hypothesized that complexation with RALA could similarly be used to conceal a BP's hydroxyapatite affinity, and to enhance bioavailability, thereby improving anticancer efficacy. Incubation of RALA with alendronate, etidronate, risedronate, or zoledronate provoked spontaneous electrostatic formation of cationic nanoparticles that did not exceed 100 nm in diameter and that were stable over a range of temperatures and for up to 6 h. The nanoparticles demonstrated a pH responsiveness, possibly indicative of a conformational change, that could facilitate release of the BP cargo in the endosomal environment. RALA/BP nanoparticles were more potent anticancer agents than their free BP counterparts in assays investigating the viability of PC3 prostate cancer and MDA-MB-231 breast cancer cells. Moreover, RALA complexation potentiated the tumor growth delay activity of alendronate in a PC3 xenograft model of prostate cancer. Taken together, these findings further validate the use of BPs as repurposed anticancer agents.

Characterization of High-Performance Organic Dyes for Dye-Sensitized Solar Cell: A DFT/TDDFT Study

Dye-sensitized solar cell (DSSC) is currently a promising technology that makes solar energy efficient and cost-effective to harness. In DSSC, metal free dyes, such indoline-containing D149 and D205, are proved to be potential alternatives for traditional metal organic dyes. In this work, a DFT/TDDFT characterization for D149 and D205 were carried out using different functionals, including B3LYP, MPW1K, CAM-B3LYP and PBE0. Three different conformers for D149 and four different conformers for D205 were identified and calculated in vacuum. The performance of different functionals on calculating the maximum absorbance of the dyes in vacuum and five common solvents (acetonitrile, chloroform, ethanol, methanol, and THF) were examined and compared to determine the suitable computational setting for predicting properties of these two dyes. Furthermore, deprotonated D149 and D205 in solvents were also considered, and the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were calculated, which elucidates the substitution effect on the rhodanine ring of D149 and D205 dyes on their efficiency. Finally, D149 and D205 molecules were confirmed to be firmly anchored on ZnO surface by periodic DFT calculations. These results would shed light on the design of new highly efficiency metal-free dyes.

Activated lignin‒chitosan extruded blends for efficient adsorption of methylene blue

This work investigates the production of activated lignin-chitosan extruded (ALiCE) pellets with controlled particle size distribution (almost spherical: dp ~500‒1000µm) for efficient methylene blue adsorption. The novel preparation method employed in this study successfully produced activated lignin-chitosan pellets. Structural and morphological characterizations were performed using BET, FTIR and SEM-EDX analyses. The influence of contact time, solution pH, ionic strength, initial adsorbate concentration and desorption studies was investigated. The experimental data fitted well with the Langmuir isotherm (R2 = 0.997), yielding a maximum adsorption capacity of 36.25mg/g. The kinetic data indicated that methylene blue (MB) adsorption onto ALiCE can be represented by the pseudo second-order-model with intraparticle processes initially controlling the process of MB adsorption. Overall, these results indicate that the novel ALiCE offers great potential for removing cationic organic pollutants from rivers and streams.

Cationic Bovine Serum Albumin (CBA) conjugated Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles for extended delivery of methotrexate into brain tumor

Current treatment strategies for the treatment of brain tumor have been hindered primarily by the presence of highly lipophilic insurmountable blood-brain barrier (BBB). The purpose of current research was to investigate the efficiency of engineered biocompatible polymeric nanoparticles (NPs) as drug delivery vehicle to bypass the BBB and enhance biopharmaceutical attributes of anti-metabolite methotrexate (MTX) encapsulated NPs. The NPs were prepared by solvent diffusion method using cationic bovine serum albumin (CBA), and characterized for physicochemical parameters such as particle size, polydispersity index, and zeta-potential; while the surface modification was confirmed by FTIR, and NMR spectroscopy. Developed NPs exhibited zestful relocation of FITC tagged NPs across BBB in albino rats. Further, hemolytic studies confirmed them to be non-toxic and biocompatible as compared to free MTX. In vitro cytotoxicity assay of our engineered NPs on HNGC1 tumor cells proved superior uptake in tumor cells; and elicited potent cytotoxic effect as compared to plain NPs and free MTX solution. The outcomes of the study evidently indicate the prospective of CBA conjugated poly (D,L-lactide-co-glycolide) (PLGA) NPs loaded with MTX in brain cancer bomber with amplified capability to circumvent BBB.