title: Co-delivery of 10-hydroxycamptothecin with doxorubicin conjugated prodrugs for enhanced anticancer efficacy.
abstract: Well-defined amphiphilic linear-dendritic prodrugs (MPEG-b-PAMAM-DOX) are synthesized by conjugating doxorubicin (DOX), to MPEG-b-PAMAM through the acid-labile hydrazone bond. The amphiphilic prodrugs form self-assembled nanoparticles in deionized water and encapsulate the hydrophobic anticancer drug 10-hydroxycamptothecin (HCPT) with a high drug loading efficiency. Studies on drug release and cellular uptake of the co-delivery system reveal that both drugs are released in a pH-dependent manner and effectively taken up by MCF-7 cells. In vitro methyl thiazolyl tetrazolium (MTT) assays and drug-induced apoptosis tests demonstrate the HCPT-loaded nanoparticles suppress cancer cell growth more efficiently than the MPEG-b-PAMAM-DOX prodrugs, free HCPT, and physical mixtures of MPEG-b-PAMAM-DOX and HCPT at equivalent DOX or HCPT doses.
authors: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors: Yu
authors: Y
authors: Zhang
authors: Chunsheng
authors: C
authors: Xiao
authors: Mingqiang
authors: M
authors: Li
authors: Jie
authors: J
authors: Chen
authors: Jianxun
authors: J
authors: Ding
authors: Chaoliang
authors: C
authors: He
authors: Xiuli
authors: X
authors: Zhuang
authors: Xuesi
authors: X
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; C104700:PAMAM Starburst; D011355:Prodrugs; D011092:Polyethylene Glycols; D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol; C028098:10-hydroxycamptothecin; D002166:Camptothecin