WITHDRAWN: Magnetic and CD44 receptor dual targeting redox-responsive polymeric micelle for precise delivery of Gambogic acid to triple-negative breast cancer

Abstract Gambogic acid (GA) is a naturally anticancer drug, which exuded from the Garcinia hanburyi tree , with extremely poor aqueous solubility and biosafety. Tumor-targeted drug delivery is considered as a promising approach to reduce the toxicity and increase the efficacy of GA. In this study, a novel tumor magnetic and CD44 receptor dual targeting redox-responsive multifunctional polymeric micelle (mPEG-HA/CSO-SS-Hex/Fe 3 O 4 /GA), which consists of a reduciblehexadecanol-modified chitosan oligosaccharide polymeric micelle (CSO-SS-Hex) coated with mono-aminated poly (ethylene glycol) grafted hyaluronic acid (mPEG-HA) and loaded with GA and Fe 3 O 4 nanoparticles, was developed for parenteral delivery GA for the treatment of triple negative breast cancer (TNBC). The complex micelles were characterized by their particle size and morphology, zeta potential, hysteresis loop, encapsulation efficiency and in vitro drug release. Meanwhile investigated the cytotoxicity, TNBC cellular uptake study and bio- distribution, antitumor activity of the formulations. All results indicated that the mPEG-HA/CSO-SS-Hex/Fe 3 O 4 /GA micelle was an excellent polymeric micelle for double-targeted (magnetic and CD44 receptor target) GA delivery and intelligent drug release (redox-responsive in high glutathione (GSH)) to TNBC with remarkable curative effect. In conclusion, the tumor magnetic and CD44 receptor dual targeting redox-responsive multifunctional magnetic polymeric micelle (mPEG-HA/CSO-SS-Hex/Fe 3 O 4 /GA) has the potential to be an effective carrier in targeted drug delivery for the TNBC chemotherapy.