Hydroxybutyl chitosan oligosaccharide-coated hemocompatible nanoparticles for controlled drug release

Objectives Hemocompatibility and controlled release properties are critical factors in designing drug delivery systems to enhance efficacy in cancer therapy. This study aimed to design thermal/pH dual-responsive core-shell nanoparticles (CSNPs) by coating casein cores with biocompatible thermo-responsive hydroxybutyl chitosan oligosaccharide (HBCOS) and to evaluate their potential for doxorubicin (DOX) delivery. Methods CSNPs were prepared by coating casein cores with HBCOS, and characterized for diameter, morphology and nuclear magnetic resonance. Their hemocompatibility was assessed by incubation in erythrocytes and 10% fetal bovine serum (FBS). DOX-loaded CSNPs were evaluated for in vitro release under different pH and temperature conditions. Cytotoxicity and intracellular DOX release were examined in HT-29 cells at 37 °C and 42 °C, and nuclear colocalization was analyzed. Results The CSNPs exhibited excellent hemocompatibility, as demonstrated by the absence of aggregation upon incubation in 10% FBS and the lack of hemolysis upon incubation with erythrocytes. Furthermore, compared with free DOX, the DOX-loaded CSNPs significantly prolonged blood circulation and increased the absorption of DOX. The initial release rate and cumulative release of DOX from CSNPs were significantly increased under conditions of decreased pH and increased temperature, demonstrating thermal/pH dual-responsive release. The reduced cell viability of HT-29 cells incubated with DOX-loaded CSNPs at 42 °C compared with those incubated at 37 °C confirmed the thermo-sensitive cytotoxicity of the loaded nanoparticles. Furthermore, the acidic intracellular environment of tumor cells and elevated temperature promoted intracellular release of DOX from CSNPs and its colocalization in the nucleus, facilitating enhanced antitumor activity. Conclusions DOX-loaded CSNPs with excellent hemocompatibility and thermal/pH-responsive release properties may serve as a promising drug delivery system for cancer therapy.