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Co‐delivery of 10‐Hydroxycamptothecin with Doxorubicin Conjugated Prodrugs for Enhanced Anticancer Efficacy
Author(s) -
Zhang Yu,
Xiao Chunsheng,
Li Mingqiang,
Chen Jie,
Ding Jianxun,
He Chaoliang,
Zhuang Xiuli,
Chen Xuesi
Publication year - 2013
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201200441
Subject(s) - prodrug , doxorubicin , conjugated system , chemistry , combinatorial chemistry , anticancer drug , pharmacology , stereochemistry , drug , biochemistry , organic chemistry , chemotherapy , medicine , polymer , surgery
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.