Nanoscale Coordination Polymers Codeliver Carboplatin and Gemcitabine for Highly Effective Treatment of Platinum-Resistant Ovarian Cancer

作者：Poon Christopher; Duan Xiaopin; Chan Christina; Han Wenbo; Lin Wenbin^*

来源：Molecular Pharmaceutics, 2016, 13(11): 3665-3675.

DOI：10.1021/acs.molpharmaceut.6b00466

• nanoscale coordination polymers
• carboplatin
• gemcitabine
• synergistic effect
• platinum-resistant ovarian cancer

Due to the ability of ovarian cancer (OCa) to acquire drug resistance, it has been difficult to develop efficient and safe chemotherapy for OCa. Here, we examined the therapeutic use of a new self-assembled core shell nanoscale coordination polymer nanoparticle (NCP-Carbo/GMP) that delivers high loadings of carboplatin (28.0 +/- 2.6 wt %) and gemcitabine monophosphate (8.6 +/- 1.5 wt %). A strong synergistic effect was observed between carboplatin and gemcitabine against platinum-resistant OCa cells, SKOV-3 and A2780/CDPP, in vitro. The coadministration of carboplatin and gemcitabine in the NCP led to prolonged blood circulation half-life (11.8 +/- 4.8 h) and improved tumor uptake of the drugs (10.2 +/- 4.4% ID/g at 24 h), resulting in 71% regression and 80% growth inhibition of SKOV-3 and A2780/CDDP tumors, respectively. Our findings demonstrate that NCP particles provide great potential for the codelivery of multiple chemotherapeutics for treating drug-resistant cancer.

• 出版日期2016-11