In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers

Di Li,^1,2,* Jian Xun Ding,^1,3,* Zhao Hui Tang,¹ Hai Sun,¹ Xiu Li Zhuang,¹ Jing Zhe Xu,² Xue Si Chen<sup>1

1</sup>Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, ²Department of Chemistry, Yanbian University, Yanji, ³Graduate University of Chinese Academy of Sciences, Beijing, China
^*These authors contributed equally to this work

Abstract: Four monomethoxy poly(ethylene glycol)-poly(L-lactide-co-glycolide)2 (mPEG-P(LA-co-GA)2) copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with double hydroxyl functionalized mPEG (mPEG-(OH)2) as macroinitiator and stannous octoate as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer at pH 7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by content of hydrophobic polyester and pH of the release medium. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of P(LA-co-GA), and the nanomedicines displayed effective proliferation inhibition against Henrietta Lacks’s cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio of DOX significantly. These results suggested that the novel anticancer nanomedicines based on DOX and amphiphilic Y-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo, with enhanced stability during circulation and accelerated drug release at the target sites.

Keywords: amphiphilic Y-shaped copolymer, anticancer nanomedicine, cellular proliferation inhibition, doxorubicin