Drug-induced hierarchical self-assembly of poly(amino acid) for efficient intracellular drug delivery

As a potent anticancer drug, gambogic acid (GA) suffers from its poor water solubility and low chemical stability and shows a limited clinical outcome. To address this problem, we report here a simple and effective strategy to immobilize and deliver GA using a reducible diblock poly(amino acid) as a model. The electrostatic interaction between GA and polymer enables a high drug loading content up to 53.6%. Moreover, the drug complexation induces a micelle-to-vesicle transformation, combined with a conformation transition from random coil to ?-helix. The hierarchically assembled drug nanocomplexes can serve as a smart carrier for efficient cell internalization and triggered release of multiple drugs under intracellular acidic and reductive conditions, resulting in a synergistic antitumor efficacy in vitro. This work provides a new insight into the drug-carrier interaction and a facile nanoplatform for drug delivery applications. ? 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.