title: Biodegradable block copolymer-doxorubicin conjugates via different linkages: preparation, characterization, and in vitro evaluation.
abstract: Doxorubicin (Dox) was conjugated onto a biodegradable block copolymer methoxy-poly(ethylene glycol)-block-poly(lactide-co-2,2-dihydroxymethylpropylene carbonate (mPEG-b-P(LA-co-DHP)) via a carbamate linkage and an acid-labile hydrazone linkage, respectively. Mutifunctional mixed micelles consisting of Dox-containing copolymer mPEG-b-P(LA-co-DHP/Dox) and folic acid-containing copolymer mPEG-b-P(LA-co-DHP/FA) were successfully prepared by coassembling the two component copolymers. The mixed micelles had well-defined core shell structure and their diameters were in the range of 70-100 nm. Both Dox-conjugates (via carbamate or hydrazone linkage) showed pH-dependent release behavior, and the micelles with hydrazone linkage showed more pH-sensitivity compared to those with carbamate linkage. The in vitro cell uptake experiment by CLSM and flow cytometry showed preferential internalization of FA-containing micelles by human ovarian cancer cell line SKOV-3 than that without FA. Flow cytometric analysis was conducted to reveal the enhanced cell apoptosis caused by the FA-containing micelles. These results suggested that these micelles containing both chemotherapeutic and targeting ligand could be a promising nanocarrier for targeting the drugs to cancer cells and releasing the drug molecules inside the cancer cells.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Hu
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D011108:Polymers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D004317:Doxorubicin