(269c) Platinum Nanoparticles Encapsulated within PLGA, Treatment for TNBC, an in Vitro and In Vivo study

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 their 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 triple negative breast cancer (TNBC) based on Pt NPs. TNBC is a type of breast cancer that lacks the three common receptors used for immunotherapy and with a tendency to metastasize faster. Therefore, TNBC has a worst prognosis and often chemotherapy is the only treatment option. However, chemotherapy is toxic, has many side effects and some cancers can even develop resistance, therefore, new treatment options are needed to combat TNBC.

Drug delivery systems are technologies that help enhance circulation time or targeting at the tumor site. Therefore, to avoid accumulation in the liver or spleen a drug 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. Moreover, to enhance the circulation lifetime of the particles, surface modifications with polymers such as polyethylene glycol (PEG) can be performed. Surface modifications with PEG are a commonly used procedure to enhance circulation-time. Furthermore, active targeting by ligands of specific biomarkers, monoclonal antibodies, peptides, and aptamers provides the most effective therapy. TNBC 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 in vitro 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 with PEG and EGFR were performed to increase circulation time, and achieve a higher anticancer effect. Different combinations of PEG/EGFR were synthesized and tested in vitro with TNBC, achieving a better efficacy using 50% PEG and 50% EGFR on particles surface. Based on the promising results achieved in vitro, the effect of bare PtNPs and 50% EGFR PtNPs were tested in vivo with mice. 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.