title: Amphiphilic polycarbonate conjugates of doxorubicin with pH-sensitive hydrazone linker for controlled release.
abstract: Novel amphiphilic polycarbonates-graft-doxorubicin (mPEG-b-P(ATMC-co-DTC)-g-DOX) were successfully designed and synthesized for pH-triggered intercellular drug release in cancer cells. The amphiphilic block copolymer, mPEG-b-P(ATMC-co-DTC), was synthesized in bulk using immobilized porcine pancreas lipase (IPPL) as the catalyst. After allyl epoxidation of ATMC units, DOX was covalently conjugated to the hydrophobic polycarbonates block through a hydrazone linkage. The resulting mPEG-b-P(ATMC-co-DTC)-g-DOX prodrugs could self-assemble to form nano-sized micelles in aqueous solution, while DOX contents in the hydrophobic core were 9.9 and 12.5 wt.%. DOX release rate from the prodrug micelles increased in acidic medium due to the acid-cleavable hydrazone linkage between the DOX and polycarbonates. MTT assays demonstrated that DOX prodrug micelles in this study showed effective cytotoxic effects to HeLa cells. Furthermore, confocal laser scanning microscopy (CLSM) observations also revealed that mPEG-b-P(ATMC-co-DTC)-g-DOX prodrugs could efficiently deliver and release DOX into the nuclei of HeLa cells.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: You-Mei
authors.initials: YM
authors.lastname: Li
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Yin-Jia
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China. Electronic address: fenghe2002@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D010316:Particle Size; D011076:Polycarboxylate Cement / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D013501:Surface-Active Agents / Q000737:chemistry*; D034421:Sus scrofa
chemical_list: D003692:Delayed-Action Preparations; D006835:Hydrazones; D008823:Micelles; D011076:Polycarboxylate Cement; D011355:Prodrugs; D013501:Surface-Active Agents; C005506:polycarbonate; D011092:Polyethylene Glycols; D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol
keywords: Controlled release; Doxorubicin; Polycarbonates; Prodrugs; pH-sensitive