(350x) Drug Delivery System for Platinum Nanoparticles, Anticancer Agent for Triple Negative Breast Cancer with Low Toxicity

Breast cancer is the second leading cause of cancer death for women. It is classified based on the overexpression of receptors on the cancer cell membrane. Targeted therapies to these receptors have decreased the mortality of certain breast cancers. Current therapies target the overexpression of progesterone (PR), estrogen (ER) or human epidermal growth factor 2 (HER2). In addition, chemotherapy, surgery, or radiation are often combined to increase the effectivity of the treatment. However, 10-19% of breast cancers are triple negative, defined by the lack of these three receptors. Moreover, triple negative breast cancer (TNBC) tends to metastasize faster than other kinds of breast cancer, resulting in a worse prognosis and often chemotherapy as the only treatment for metastasis. Many cancer patients need to abort chemotherapy due to complications arising from its side effects, and this is a primary contributor to mortality. Therefore, new treatment options need to be developed for TNBC with low toxicity to healthy cells.

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 (Pt NPs) 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 Pt NPs. PLGA is a copolymer of poly(lactic acid) (PLA) and poly(glycolic acid) (PGA), those two monomers are metabolized by the body, making PLGA toxicity minimal. The encapsulation of Pt NPs within PLGA nanoparticles was performed by three different methodologies: nanoemulsion, electrohydrodynamic co-jetting and nanoprecipitation.

Pt NPs anticancer activity was tested performing cell viability experiments with TNBC and comparing with a common chemotherapeutic drug (cisplatin). As the major drawback of 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. Encapsulation of Pt NPs within PLGA was performed by three different methodologies. The highest encapsulation rate was achieved by nanoemlusion with a 60% loading percentage. In summary this work provides a new treatment for TNBC based on Pt NPs with no apparent toxicity for healthy cells, overcoming one of the major drawbacks of current treatments.