Synthesis of a new triple-responsive biocompatible block copolymer: Self-assembled nanoparticles as potent anticancer drug delivery vehicle

There has been a continuous effort towards a synthesis of new stimuli-responsive polymer nanoparticle systems for improved cancer chemotherapy over the last decade. In this context, we have presently developed a temperature, pH, and redox-responsive amphiphilic block-copolymer capable of forming nanoparticles in the aqueous medium, targeted towards drug delivery applications. The copper-catalyzed azide-alkyne cycloaddition reaction was utilized to fie the ends of two copolymers - a thermo-responsive poly(N-iso-propylacrylamide) based copolymer with an azide end group and a pH-responsive hydrophobic polymer with redox responsive disulfide bond and an alkyne end group, producing a new triple responsive amphiphilic block copolymer (PHNP) that self-assemble in water to produce nanoparticles. Upon heating above the cloud point of poly(N-isopropylacrylamide), these nanoparticles experienced further aggregation to produce larger sized particles as measured by dynamic light scattering, UV-visible spectroscopy, and scanning electron microscopy techniques. PHNP was found to be capable of encapsulating drugs like doxorubicin (DOX) and also fluorescent probes alike Nile Red. The drug release kinetics divulged that in a period of 24 h more than 90% of the encapsulated DOX was released in pH 5.4 buffer having 10 mM glutathione (GSH) at 40 degrees C, an environment prevailing in cancer tissues. In vitro studies including live-dead assay and rhodamine-DAPI staining showed that PHNP was non-cytotoxic. DOX-loaded PHNP was observed to be more effective in prohibiting bone cancer cell (MG63) line in comparison to free DOX, demonstrated by the significant reduction of IC50 values. The uptake studies showed that DOX-encapsulated PHNP was more effective for morphometric distortion of MG63 cells in comparison to bare DOX. Therefore, the present research on the development of a biocompatible thermal, pH, and redox-responsive polymer opens up new opportunities in the area of polymeric carrier systems for drug delivery to cancer cells.