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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.

ABSTRACT: 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.

SUBMITTER: Sang MM

PROVIDER: S-EPMC6225507 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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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.

Sang Mang Mang MM Liu Fu Lei FL Wang Yang Y Luo Ren Jie RJ Huan Xiao Xian XX Han Ling Fei LF Zhang Zhong Tao ZT Feng Feng F Qu Wei W Liu Wenyuan W Zheng Feng F

Drug delivery 20181101 1

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 Fe3 ...[more]

PMID: 30334478

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Dataset Information

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.

Publications

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.

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