Reactive oxygen species-responsive amino acid-based polymeric nanovehicles for tumor-selective anticancer drug delivery

Abstract Stimuli-triggered drug delivery systems have been recognized as a crucial strategy to achieve on-demand drug release at the tumor for improving therapeutic efficacy. In this work, novel biocompatible and biodegradable reactive oxygen species (ROS)-responsive amino acid- based polymeric micelles were developed for tumor-specific drug release triggered by high ROS levels in cancer cells, which were composed of amphiphilic poly(aspartic acid) (PASP) derivatives (PASP-BSer) with phenylborate serine (BSer) side groups as the ROS-responsive unit. A series of PASP-BSer conjugates with different degree of substitution (DS) were synthesized, and their self-assembly and H2O2-responsive behaviors were investigated to optimize the structure of PASP-BSer. In vitro drug loading and release studies confirmed that the optimized PASP-BSer micelles could effectively encapsulate the model anticancer drug doxorubicin (Dox) and exhibit desirable H2O2-triggered release behaviors. More importantly, Dox-loaded PASP-BSer micelles showed high selective cytotoxicity against A549 cancer cells than L929 normal cells. Accordingly, PASP-BSer micelles have significant potential as on-demand drug carriers for anticancer therapy.