Ovarian cancer is a deadly disease that afflicts approximately 22,000 women per year in the US. Once the disease reaches stage III and has metastasized to the abdominal cavity, the 5-year survival rate is only 34%. Our goal is to develop stem cell/nanoparticle hybrids for targeted and selective tumor killing in patients suffering from late stage ovarian cancer. Neural Stem Cells (NSCs) are appealing for use as targeted delivery platforms in the abdomen, as they have demonstrated inherent tumor tropic properties to ovarian cancer cells in vitro and in vivo following IP administration. However, NSCs do not intrinsically have any anti-tumor efficacy. As NSC-based therapy moves into the clinic, there is a need to develop complementary techniques to enable targeted delivery of chemotherapeutics by NSCs. An attractive complementary approach involves the use of nanoparticles (NPs), which can be loaded with a broad spectrum of chemotherapeutic agents for delivery and dissemination at tumor sites. Therefore, we are developing delayed-drug release NP/NSC constructs to realize a modular and general drug targeting system. Here, we synthesized a small library of model fluorescent silica NPs (SiNPs) with various surface functional groups, as well as cisplatin-loaded therapeutic silica NPs. The SiNPs were characterized by TEM, SEM, DLS, zetasizer, and the amount of Pt was quantified by ICP-MS. In vitro efficacy tests of these cisplatin-NPs demonstrated delayed drug release over 3 days. We then treated NSCs with cisplatin-NPs and injected these NSC-NP hybrids in mice bearing ovarian cancer tumors. In this biodistribution study, the amount of Pt in tumors and organs were quantified by ICP-MS 24h post injection. Our data demonstrated that NSC-NP hybrids have much superior accumulation of Pt in tumors than both free cisplatin and free cisplatin-NPs. Current work focuses on the long term survival of ovarian cancer-bearing mice treated with NSC-NP hybrids.

Using neural stem cell: Nanoparticle constructs to selectively deliver therapeutics to ovarian cancer

251st National Meeting (2016)

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