Grant: Travel Awards - Institute Community Support

Triple negative breast cancer (TNBC) constitutes 10% - 20% of all breast cancer and is associated with high risk of metastasis and poor prognosis. Chemotherapy is mainly used to treat TNBC with good response rate but frequent relapse and shorter survival time compared to other subtypes of breast cancer. A protein receptor named alphavbeta3 integrin is overexpressed on the surface of the TNBC cells and tumor blood vessel cells compared to normal cells. This characteristic of cancer cells can be targeted by coating RGD peptide molecules onto the surface of our developed nanoparticle system loaded with two chemotherapeutic drugs doxorubicin (DOX) and mitomycin C (MMC) that work in synergy. The RGD coated nanoparticles can then bind to the cancer cells and tumor vasculature more readily compared to non-cancerous cells, achieving tumor specific targeting and further enhanced the anticancer efficacy compared to the non-targeted nanoparticles. Our study aimed to synthesize this metastasis-specific RGD peptide coated DOX and MMC co-loaded nanoparticles (RGD-DMNPs) and evaluate its efficacy and safety both at the cell level and in mice model with human TNBC. RGD-DMNPs have exhibited enhanced cytotoxicity against a TNBC cell line in cell culture compared to non-targeted nanoparticles and free drugs solution. The imaging dye-labeled active-targeted nanoparticles showed significantly higher accumulation in the metastasis-bearing lung of the mice compared to non-targeted nanoparticles based on the imaging study. Most importantly, RGD peptide coating significantly improved the efficacy of the drugs-loaded nanoparticles with 5-fold and 31-fold reduction in tumor burden and prolonged mean survival time by 31% and 61%, as compared to non-targeted DMNPs and free drugs, respectively without noticeable toxicity to heart and liver.