Enzyme and pH dual responsive l‐amino acid based biodegradable polymer nanocarrier for multidrug delivery to cancer cells

We report a new pH and enzyme dual responsive biodegradable polymer nanocarrier to deliver multiple anticancer drugs at the intracellular compartment in cancer cells. Natural l-aspartic acid was converted into multifunctional monomer and polymerized to yield new classes of biodegradable aliphatic polyester in-build with pH responsiveness. The transformation of side chain BOC urethanes into cationic NH3+ in the acidic endosomal environment disassembled the polymers nanoparticles (pH trigger-1). The biodegradation of aliphatic polyester backbone by esterase enzyme ruptured the nanoassemblies and released the drugs in the cytoplasm (trigger-2). The polymer scaffolds were capable of delivering multiple drugs such as doxorubicin, topotecan, and curcumin (CUR). The cytotoxicity of the nascent and drug-loaded nanoparticles were tested in cervical (HeLa) and breast (MCF-7) cancer cell lines. The nascent polymer nanoscaffolds were found to be nontoxic to cells whereas their drug-loaded nanoparticles exhibited excellent killing. Confocal microscopic images revealed that the drug-loaded polymer nanoparticles were taken up by the cells and the dual degradation process delivered the drugs to nucleus and established the proof-of-concept. The present investigation opens up new platform for l-amino acid based polyester scaffolds, for the first time, in the intracellular drug delivery in cancer treatment. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3279–3293