Journal
MOLECULAR PHARMACEUTICS
Volume 13, Issue 11, Pages 3665-3675Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.6b00466
Keywords
nanoscale coordination polymers; carboplatin; gemcitabine; synergistic effect; platinum-resistant ovarian cancer
Funding
- NIH [UO1-CA198989]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
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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.
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