Development of 3-in-1 nanotherapeutic strategies for ovarian cancer

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/604002v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1c2d3e3org.highwire.dtl.DTLVardef@1e4e73eorg.highwire.dtl.DTLVardef@109aceeorg.highwire.dtl.DTLVardef@387843_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOTOCC_FLOATNO C_FIG Among gynecological cancers, ovarian cancer causes the most fatality. Platin-based chemotherapy is the primary therapeutic option, but it is limited by a variety of drug resistance mechanisms. Ovarian cancer is a complex and challenging disease to treat, and combination approaches have shown stronger efficacy than a single drug alone. However, they still need to overcome challenges, such as the non-selective distribution of drugs, and side effects caused by each drug in the combination. To overcome these issues, here we explored a 3-in-1 combination nanotherapeutic approach containing cisplatin, olaparib, and metformin for ovarian cancer. To encapsulate hydrophilic cisplatin and metformin inside the nanoparticle (NP) core, we developed cisplatin polymer prodrugs and metformin derivatives. Our results showed successful development of 3-in-1 NPs containing cisplatin, olaparib, and metformin, and they are stable in the physiological conditions. In vitro evaluation showed each agent in the 3-in-1 NPs is active and exerts therapeutic effects, contributing to ovarian cancer cell killing at lower concentrations. These results provide insight into developing novel nanotherapeutic strategies for improving ovarian cancer treatment.