title: Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive shell crosslinked micelles loading disulfiram.
abstract: Metastasis, the main cause of cancer related deaths, remains the greatest challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti-tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles to achieve intracellular targeted delivery and finally inhibit tumor growth and metastasis. The crosslinked micelles demonstrated good stability in circulation and specifically released DSF under a reductive environment that mimicked the intracellular conditions of tumor cells. As a result, the DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell proliferation, induced cell apoptosis and suppressed cell invasion, as well as impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate in tumor tissue and stay there for a long time, thereby causing significant inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1 tumors. These results suggested that DCMs could be a promising delivery system in inhibiting the growth and metastasis of breast cancer.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Xiaopin
authors.initials: X
authors.lastname: Duan
authors.forename: Jisheng
authors.initials: J
authors.lastname: Xiao
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Shirui
authors.initials: S
authors.lastname: Mao
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004221:Disulfiram / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary*; D008298:Maleates / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010084:Oxidation-Reduction / Q000187:drug effects*; D011137:Polystyrenes / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D008298:Maleates; D008823:Micelles; D011137:Polystyrenes; C521900:poly(styrene-co-maleic anhydride); D004221:Disulfiram