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

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.

High gene delivery efficiency of alkylated low-molecular-weight polyethylenimine through gemini surfactant-like effect.

To our knowledge, the mechanism underlying the high transfection efficiency of alkylated low-molecular-weight polyethylenimine (PEI) is not yet well understood. In this work, we grafted branched PEI (molecular weight of 1,800 Da; bPEI1800) with lauryl chains (C12), and found that bPEI1800-C12 was structurally similar to gemini surfactant and could similarly assemble into micelle-like particles. Stability, cellular uptake, and lysosome escape ability of bPEI1800-C12/DNA polyplexes were all greatly enhanced after C12 grafting. bPEI1800-C12/DNA polyplexes exhibited significantly higher transfection efficiency than Lipofectamine 2000 in the presence of serum. Bioluminescence imaging showed that systemic injection of bPEI1800-C12/DNA polyplexes resulted in intensive luciferase expression in vivo and bioluminescence signals that could be detected even in the head. Altogether, the high transfection efficacy of bPEI1800-C12 was because bPEI1800-C12, being an analog of gemini surfactant, facilitated lysosome escape and induced the coil-globule transition of DNA to assemble into a highly organized micelle-like structure that showed high stability.