Premium
Co‐ D elivery of Oxaliplatin and Demethylcantharidin via a Polymer–Drug Conjugate
Author(s) -
Wang Enhui,
Xiong Hejian,
Zhou Dongfang,
Xie Zhigang,
Huang Yubin,
Jing Xiabin,
Sun Xinhua
Publication year - 2014
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.201300402
Subject(s) - oxaliplatin , cytotoxicity , conjugate , chemistry , internalization , biophysics , cancer cell , drug delivery , combinatorial chemistry , biochemistry , in vitro , cell , cancer , biology , organic chemistry , colorectal cancer , mathematical analysis , genetics , mathematics
A Pt (IV) complex which combined the bioactivities of both oxaliplatin and demethylcantharidin (DMC) is synthesized and delivered by a polymer–drug conjugate for combination chemotherapy. Oxaliplatin is released from the polymer–drug conjugate within cancer cell by reduction to attack nuclear DNA, while a dose of DMC is also hydrolyzed subsequently to block DNA damage‐induced defense mechanisms by serine/threonine phosphatase 2A (PP2A) inhibition. In vitro evaluation shows that the polymer–drug conjugate with dual modes of action upon cancer cells displays higher cytotoxicity against SKOV‐3 cells than that of free drugs. This enhanced cytotoxicity is attributed to the synergistic effect between oxaliplatin and DMC, as well as the effective intracellular internalization of the micelles observed by confocal laser scanning microscopy (CLSM) imaging.