title: Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles.
abstract: In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: MaLing
authors.initials: M
authors.lastname: Gou
authors.forename: HuaShan
authors.initials: H
authors.lastname: Shi
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Ke
authors.initials: K
authors.lastname: Men
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Zheng
authors.forename: ZhiYong
authors.initials: Z
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.forename: ZhiYong
authors.initials: Z
authors.lastname: Qian
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: YuQuan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004317:Doxorubicin / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008823:Micelles; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C502908:poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol); D011092:Polyethylene Glycols; D004317:Doxorubicin