Synthesis and anti-cancer drug loading properties of acetylated dextran-grafted lysine-arginine-based polyesteramide comb graft copolymer micelles

The poor water solubility of anticancer drugs significantly limits their therapeutic efficacy. Amphiphilic micelles with hydrophilic shells have emerged as promising anticancer drug carriers due to their remarkable ability to improve drug bioavailability. In this study, a Lysine-Arginine polyesteramide containing pendant carboxyl groups was synthesized (Lys-Arg-PEA). Subsequently, a series of amphiphilic comb-like copolymer micelle (AcDex-Lys-Arg-PEA) was developed through combination with acetylated dextran derivatives of different substitution degrees. The results revealed that the blank micelles maintained stable spherical structures with a uniform size distribution. The micellar system exhibited favorable hemocompatibility (hemolysis rate <5% and protein adsorption <30%), negligible cytotoxicity (cell viability >90% at 80 μg/mL concentration) and enzymatic degradability. Curcumin (Cur) was employed as a model drug to evaluate the anticancer drug delivery potential of this system. The micelles achieved high encapsulation efficiency (63%–85%) and drug loading capacity. Cur-loaded micelles showed significant inhibitory effects on HeLa cells (cell viability <55% at 80 μg/mL concentration). Drug release simulations in PBS buffer revealed pH-responsive characteristics, and the micelles exhibited faster Cur release at a cancerous pH (5.4, 50%–60%) than at a physiological pH (7.4, 30%–40%). This study demonstrates the potential of the comb-like copolymer micelles as effective carriers for anticancer drug delivery, providing valuable insights for subsequent research.