A novel redox/pH dual-responsive and hyaluronic acid-decorated multifunctional magnetic complex micelle for targeted gambogic acid delivery for the treatment of triple negative breast cancer

Drug Delivery

Feng Feng¹  Zhong Tao Zhang¹  Wei Qu¹  Fu Lei Liu¹  Xiao Xian Huan¹  Mang Mang Sang²  Feng Zheng²  Yang Wang²  Ren Jie Luo²  Wenyuan Liu²  Ling Fei Han² 

[1] Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, People’s Republic of Chin;Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, People’s Republic of China;Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, People’s Republic of China;

关键词: Magnetic;    redox/pH dual-responsive;    hyaluronic acid;    gambogic acid;    TNBC;   

DOI  :  10.1080/10717544.2018.1486472

来源: publisher

【 摘 要 】

Gambogic acid (GA) is a naturally derived potent anticancer agent with extremely poor biocompatibility. In the present study, a novel of redox/pH dual-responsive multifunctional magnetic complex micelle (sPEG/HA/CSO-SS-Hex/Fe3O4/GA), which consisted of a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and DCA grafted sheddable PEG-PLL (sPEG) copolymers and loaded with gambogic acid (GA) and Fe3O4 nanoparticles were developed for parenteral delivery for the treatment of triple negative breast cancer (TNBC). The ex vivo study showed that the sPEG shielded cationic HA/CSO-SS-Hex/Fe3O4/GA core at physiological pH but quickly shed off to re-expose the core due to its charge reversible property. The sPEG/HA/CSO-SS-Hex/Fe3O4/GA micelles effectively facilitated tumor-targeted GA delivery by HA, which is a targeting ligand for CD44 receptor of TNBC cells, meanwhile increase GA uptake at the acidic condition but diminished the drug uptake at neutral pH. The in vitro cellular uptake study and in vivo biodistribution and antitumor activity of the formulations were determined, all results showed that the complex micelle enhanced TNBC tumor cellular uptake and fast drug release due to the combined effect of magnet targeting, CD44 receptor-mediated internalization and redox/pH dual-responsive drug release. Hence, tumor-targeted delivery of GA with redox/pH dual-responsive multifunctional magnetic complex micelle sPEG/HA/CSO-SS-Hex/Fe3O4/GA might have potential implications for the chemotherapy of TNBC.

【 授权许可】

CC BY