Multi-responsive polymeric nanocarriers are emerging as smart carriers for anticancer drugs or genes to enhance the efficacies in cancer therapy. Internal as well as external stimuli, such as temperature, pH, enzymes, reductive and magnetic field were applied to disassemble the responsive polymer carriers in drug delivery. Recent studies revealed that temperature, pH and redox state of the cancer tissues are slightly different (pH &lt; 6.0 and T= 40−43 °C, concentration of glutathione &gt; 10 mM) compared to that of the normal tissues (pH 7.4 and T= 37 °C, glutathione concentration in micro level). Drugs can be selectively delivered in the cancer tissues by taking advantage of the above mentioned differential parameters. For accomplishing this goal, a new copolymer having thermoresponsiveness as well as redox and pH responsiveness was conceived. A pH responsive monomer 2-(2-((3, 4 bis(hexyloxy)benzyloxy)carbonyl)ethylthio)ethyl methacrylate (HBCEEM) was synthesized and was RAFT polymerized using a chain transfer agent (CTA) having a redox responsive alkyne group at one of the terminals. Separately, another CTA with azide end was used for synthesizing thermoresponsive poly(NIPA-r-PEGMA) (PNP) following our previous method.5 Following this, CuBr click chemistry mediated 1,3-dipolar cycloaddition was performed between azide and alkyne terminals of yhe teo polymers to form a thermo, pH, and redox triple responsive block copolymer. The block copolymer was characterized by gel permeation chromatography, NMR spectroscopy, dynamic light scattering and scanning electron microscopy. The copolymer formed self-assembled nanostructure in aqueous medium which was loaded with an anticancer drug, doxorubicin. The release of drug from this nanostructures was influenced by these three stimuli (pH, temperature, redox), with the most effective release was observed at acidic pH, at temperatures &gt; 37 °C and in presence of higher concentration of glutathione. Thus, this copolymer can be potentially useful in delivery of anticancer drugs.

Synthesis of triple-responsive, amphiphilic block copolymers for potential drug-delivery applications

2019 Spring National Meeting

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