Cancer chemotherapy is judged effective when it reduces tumor burden by blocking the proliferation and inducing apoptosis of cancer cells. In practice, often it recurs or metastasizes shortly after the primary tumor has been exterminated. Cancer stem cells are reported to be controlled by pathways that are dormant in normal adult cells, e.g. PTEN, which is a negative regulator of transcription factor STAT3. STAT3 regulates genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of significant clinical importance.This work, for the first time, reports a nanomedicine strategy for selective and safer delivery of STAT3 inhibitors designed towards metastatic and drug resistant breast cancer. We have synthesized a novel lipase-labile SN-2 phospholipids-pro-drug from a clinically investigated inhibitor, nifuroxazide, which is regioselectively cleaved by the membrane abundant enzymes in cancer cells. Pro-nifuroxazide was used to formulate the nanoparticles (Pro-nifuroxazide NP) and the cytotoxic ability of pro-nifuroxazide NP (80�5nm) was screened in ER(+)-MCF-7 and ER(-)-MD-MB231 cells at 48h-72h using MTT proliferation assay. Results indicated that pro-nifuroxazide NP are at least fivefold more effective towards inhibiting ER(+)-MCF-7-cells in a time dependent manner compared to parent nifuroxazide. This presentation will discuss the synthesis of the prodrug, its self-assembly into a nanoparticle,physico-chemical characterization of the, their cellular toxicity assays and further biological studies to confirm abolition of stem cell-subpopulation.

Regressing metastatic and drug resistant breast cancer with triggerable pronifuroxazide nanoparticle by inhibiting transcription factor STAT3

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.