Technetium-99m labeled core shell hyaluronate nanoparticles as tumor responsive, metastatic skeletal lesion targeted combinatorial theranostics.

Achieving target specific delivery of chemotherapeutics in metastatic skeletal lesions remains a major challenge. Towards this, a dual drug loaded, radiolabeled multi-trigger responsive nanoparticles having partially oxidized hyaluronate (HADA) conjugated to alendronate shell and palmitic acid core were developed. While the hydrophobic drug, celecoxib was encapsulated in the palmitic acid core, the hydrophilic drug, doxorubicin hydrochloride was linked to the shell via a pH responsive imine linkage. Hydroxyapatite binding studies showed affinity of alendronate conjugated HADA nanoparticles to bones. Enhanced cellular uptake of the nanoparticles was achieved via HADA-CD44 receptor binding. HADA nanoparticles demonstrated trigger responsive release of encapsulated drugs in the presence of hyaluronidase, pH and glucose, present in excess in the tumor microenvironment. Efficacy of the nanoparticles for combination chemotherapy was established by >10-fold reduction in IC50 of drug loaded particles with a combination index of 0.453, as compared to free drugs in MDA-MB-231 cells. The nanoparticles could be radiolabeled with the gamma emitting radioisotope technetium-99m (99mTc) through a simple, 'chelator free', procedure with excellent radiochemical purity (RCP) (>90 %) and in vitro stability. 99mTc-labeled drug loaded nanoparticles reported herein constitutes a promising theranostic agent to target metastatic bone lesions. STATEMENT OF HYPOTHESES: Technetium-99m labeled, alendronate conjugated, dual targeting, tumor responsive, hyaluronate nanoparticle for tumor specific drug release and enhanced therapeutic effect, with real-time in vivo monitoring.

Biopolymer Coating Imparts Sustainable Self-Disinfecting and Antimicrobial Properties to Fabric: Translated to Protective Gears for the Pandemic and Beyond.

The global pandemic of COVID-19 and emerging antimicrobial drug resistance highlights the need for sustainable technology that enables more preparedness and active control measures. It is thus important to have a reliable solution to avert the present situations as well as preserve nature for habitable life in the future. One time use of PPE kits is promoting the accumulation of nondegradable waste, which may pose an unforeseen challenge in the future. We have developed a biocompatible, biodegradable, and nonirritating nanoemulsion coating for textiles. The study focused on coating cotton fabric to functionalize it with broad spectrum antimicrobial, antibiofilm, and anti-SARS-CoV-2 activity. The nanoemulsion comprises spherical particles of chitosan, oleic acid, and eugenol that are cross-linked to fibers. The nanoemulsion caused complete destruction of pathogens even for the most rigid biofilms formed by drug resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans on the surface of the coated fabric. The secondary coat with beeswax imparts super hydrophobicity and 20 wash cycle resistance and leads to enhanced barrier properties with superior particulate filtration, bacterial filtration, and viral penetration efficiency as compared to an N95 respirator. The coated fabric qualifies as per standard parameters like breathability, flammability, splash resistance, and filtration efficiency for submicrometer particles, bacteria, and viruses. The scaleup and bulk manufacturing of the coating technology on fabric masks complied with standards. The consumer feedback rated the coated mask with high scores in breathability and comfortability as compared to an N95. The strategy promises to provide a long-term sustainable model compared to single use masks and PPE that will remain a nondegradable burden on the ecosystem for years to come.