(182ab) Drug Delivery System for Platinum Nanoparticles

Breast cancer is the second most common cancer among women in the United States. During the past decades mortality has declined, however it remains the second cause of death by cancer for women. The most common way of treating breast cancer is using chemotherapy, but chemotherapy has many side effects and toxicity. Currently there are different therapies that can avoid these side effects by using specific targets. Breast cancer can be classified on the expression of estrogen and progesterone receptors (ER+/PR+) and human epidermal growth factor receptor 2 (HER2+). The presence of those three receptors can be used for targeted therapies. However, not all the breast cancers are positive to these receptors, with about 19% of all the cases being triple negative (ER-/PR-/HER2-). Triple negative breast cancer does not have any targeted therapy leaving just three treatment options, surgery, radiotherapy and chemotherapy. Therefore, there is an urgent need for new therapies against triple negative breast cancer.

Cisplatin (cis-diamminedicholoroplatinum(II)) is one of the more commonly used platinum based agents. It is used in almost 50% of tumor therapies as a chemotherapy drug. But, cisplatin has several limitations and is plagued with side effects like nephrotoxicity (toxicity in the kidneys), cardiotoxicity (damage to the heart), hepatotoxicity (toxicity in the liver), and neurotoxicity (alteration of the normal activity of the nervous system). Due to the many side effects of cisplatin, less toxic platinum nanoparticles (PtNPs) are an attractive solution to overcome this toxicity problem. Nanomedicine offers the option to act selectively against cancer and enhance the effectiveness of other therapies. 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 platinum nanoparticles can be used as a therapy for cancer showing a limited toxicity to healthy cells. The activity of platinum nanoparticles can be related to the release of Pt²⁺ ions, which damage DNA via double-strand breaks causing growth arrest and apoptosis. In this work, platinum nanoparticles were synthesized adapting the work from Shim et al., to produce particles of 45nm. Triple negative breast cancer and fibroblast cells were treated with the PtNPs, showing a remarkable anticancer activity with a limited toxicity to healthy cells.

Moreover, to enhance the circulation of the particles and accumulation at the tumor site a delivery system is preferred. Poly(lactide-co-glycolide) (PLGA) particles where synthesized as a delivery system for PtNPs. 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. In this work, the encapsulation of PtNPs within PLGA particles was performed by three different methodologies: nanoemulsion, electrospinning and nanoprecipitation. By using TEM, the successful encapsulation of PtNPs inside PLGA particles of 150nm was confirmed.