(266c) Encapsulated Platinum Nanoparticles, Targeted Therapy for Triple Negative Breast Cancer

Nanotechnology is a multidisciplinary field that has many different applications including cancer treatment and detection. Noble metal nanoparticles such as gold, silver or palladium, have shown major potential in the field of medicine and pharmaceutics. In particular, platinum nanoparticles (PtNPs) have been reported with promising anticancer results. The activity of nanoparticles is based on small size and high surface area; these properties allow them to penetrate biofilms as well as influence intracellular mechanisms. Recent studies indicate that Pt NPs can be used as a therapy for cancer showing a limited toxicity to healthy cells. Hence, in this work, we developed a new treatment option for TNBC based on Pt NPs. Moreover, to enhance the circulation at the tumor site, a delivery system was proposed. Poly(lactide-co-glycolide) (PLGA) particles were synthesized as a delivery system for PtNPs. PLGA is a copolymer of poly(lactic acid) (PLA) and poly(glycolic acid) (PGA), two monomers that are metabolized by the body, making PLGA toxicity minimal. The encapsulation of PtNPs within PLGA nanoparticles was performed by nanoemulsion.

Nanoparticles that circulate in the bloodstream are recognized by proteins. Proteins attach to the surface forming a nanoparticle-protein complex (protein corona) that leads to phagocytic system recognition and removal from the bloodstream. To enhance the circulation life-time of the particles, surface modifications with some polymers such as polyethylene glycol (PEG) can be performed. Surface modifications with PEG is a commonly used procedure to enhance the properties of drug systems. Active targeting which includes antibodies attached to the surface provides the most effective therapy. Several targeted therapies can be used such as ligands of specific biomarkers, monoclonal antibodies, peptides, and aptamers. Triple negative breast cancer is defined by the lack of overexpression of the three common receptors used to classify breast cancer. Therefore, there are very few available targets. Epidermal growth factor (EGF) is a receptor that promotes cell proliferation migration and angiogenesis (development of new blood vessels). EGFR is overexpressed in many tumors including breast cancer. Therefore, many strategies based on antibodies have been studied to block EGFR. The anti-EGFR monoclonal antibody, Cetuximab, has shown promise for targeting metastatic TNBC.

In the present study, PtNPs were synthesized and the anticancer activity was tested against TNBC, showing a remarkable cell death. As the major drawback of traditional chemotherapy is the toxicity, cell viability experiments were also performed on fibroblasts. The results showed no apparent toxicity of Pt NPs for healthy cells in contrast to cisplatin (a common chemotherapeutic drug). Encapsulation of PtNPs within PLGA was performed by nanoemlusion with a 60% loading percentage. Surface modifications were performed to prevent protein corona formation and achieve a higher anticancer effect. Cytotoxicity with TNBC of PtNPs encapsulated in PLGA with active and passive targeting were compared, demonstrating a higher cell death by particles conjugated with the antibody. In summary, this work provides evidence of a potential new treatment for TNBC based on Pt NPs with no apparent toxicity for healthy cells, overcoming one of the major drawbacks of current treatments.