Improved Anti-Triple Negative Breast Cancer Effects of Docetaxel by RGD-Modified Lipid-Core Micelles

Abstract

Rujing Chen,1,2,* Shuting Ni,1,* Wangyan Chen,1 Mei Liu,3 Jianfang Feng,4 Kaili Hu1 1Murad Research Center for Modernized Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaili HuMurad Research Center for Modernized Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] FengSchool of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of ChinaEmail [email protected]: A novel RGD-modified PEGylated lipid-core micelle delivery system was designed to improve the anti-cancer effect of docetaxel on triple negative breast cancer (TNBC).Methods: The tumor-targeted lipid-core micelles loaded with docetaxel were prepared and characterized. Their morphology, particle size, zeta potential, entrapment efficiency, release profiles, and targeting effects were studied. The antitumor effects of the docetaxel-loaded nano-micelles were investigated in a MDA-MB-231 cell model in vitro and a MDA-MB-231 xenograft model in vivo.Results: The prepared RGD-modified docetaxel-loaded lipid-core micelles were spherical with a particle size of 16.44± 1.35 nm, zeta potential of − 19.24± 1.24 mV, and an encapsulation efficiency of 96.52± 0.43%. The drug delivery system showed sustained release properties and could significantly enhance docetaxel uptake by MDA-MB-231 tumor cells in vitro, which was proved to be a caveolae pathway mediated process requiring ATP, Golgi apparatus, and acid lysosomes. The results of the pharmacokinetic study displayed that the area under the curve of the targeted micelles was 3.2-times higher than that of docetaxel commercial injections. Furthermore, in a MDA-MB-231 tumor-bearing mice model, a higher antitumor efficacy than docetaxel commercial injections was displayed, and the safety experiments showed that the micellar material did not cause major organ damage after intravenous administration in mice.Conclusion: The novel RGD-modified PEGylated lipid-core micelle delivery system significantly improved the antitumor effects and reduced the side-effects of docetaxel, providing a promising therapeutics for the treatment of TNBC.Keywords: docetaxel, lipid-core micelles, RGD peptide, breast cancer therapy

Keywords

• docetaxel
• lipid-core micelles
• rgd peptide
• breast cancer therapy