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 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