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.
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Camptothecin / administration & dosage
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Camptothecin / analogs & derivatives*
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Camptothecin / pharmacology
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Cell Survival / drug effects
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Dendrimers / chemistry
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Doxorubicin / administration & dosage*
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Doxorubicin / pharmacology
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Drug Delivery Systems*
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Endocytosis / drug effects
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Flow Cytometry
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Hep G2 Cells
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Humans
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Intracellular Space / metabolism
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MCF-7 Cells
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Magnetic Resonance Spectroscopy
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Microscopy, Confocal
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Nanoparticles / chemistry
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Polyethylene Glycols / chemistry
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Prodrugs / administration & dosage*
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Prodrugs / chemical synthesis
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Prodrugs / chemistry
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Prodrugs / pharmacology*
Substances
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Antineoplastic Agents
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Dendrimers
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PAMAM Starburst
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Prodrugs
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Polyethylene Glycols
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Doxorubicin
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monomethoxypolyethylene glycol
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10-hydroxycamptothecin
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Camptothecin