PT  - JOURNAL ARTICLE
AU  - Durocher, Emma
AU  - McGrath, Sean
AU  - Gahunia, Esha
AU  - Matsuura, Naomi
AU  - Gadde, Suresh
TI  - Development of 3-in-1 nanotherapeutic strategies for ovarian cancer
AID  - 10.1101/2024.07.17.604002
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.07.17.604002
4099  - http://biorxiv.org/content/early/2024/07/22/2024.07.17.604002.short
4100  - http://biorxiv.org/content/early/2024/07/22/2024.07.17.604002.full
AB  - TOC 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.Competing Interest StatementThe authors have declared no competing interest.