Dual-action organoplatinum polymeric nanoparticles overcoming drug resistance in ovarian cancer

被引：14
作者：
Jayawardhana, Amarasooriya M. D. S. [1 ]
Qiu, Zhihan [1 ]
Kempf, Susan [1 ]
Wang, Han [1 ]
Miterko, Mitchell [1 ]
Bowers, David J. [1 ]
Zheng, Yao-Rong [1 ]
机构：
[1] Kent State Univ, Dept Chem & Biochem, 224 Williams Hall, Kent, OH 44242 USA
来源：
DALTON TRANSACTIONS | 2019年 / 48卷 / 33期
基金：
美国国家科学基金会;
关键词：
CYCLOMETALATED COMPLEXES; ANTICANCER; PLATINUM; ANTITUMOR; METALLACYCLES; METALLACAGES; DELIVERY; RELEASE; TARGET; FUTURE;
D O I：
10.1039/c9dt01683j
中图分类号：
O61 [无机化学];
学科分类号：
070301 ; 081704 ;
摘要：
Drug resistance to the conventional platinum chemotherapy remains a major challenge for treating ovarian cancer. Herein, we present a novel approach to overcome the drug resistance by utilizing "dual-action" organometallic polymeric nanoparticles (OPNPs). The OPNPs were formed by the assembly of the organoplatinum payloads and the anionic block copolymer, methoxy polyethylene glycol-block-polyglutamic acid (MPEG(5k)-PGA(50)). The OPNPs enhance the solubility and biocompatibility of the hydrophobic organoplatinum payloads. The OPNPs enter the cancer cells via endocytosis, and the payloads loaded in the core of the nanoparticles are slowly released under the acidic conditions of endosomes. Unlike conventional platinum therapeutics, the organoplatinum compound exhibits a "dual-action" attack by triggering nuclear DNA damage and mitochondrial damage. As a result, drug-resistant ovarian cancer cells become vulnerable to the organoplatinum payloads.
引用
收藏
页码：12451 / 12458
页数：8
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