Treatment of Breast Cancer with Silver Antitumor Drugs Encapsulated in Biodegradable Polymeric Nanoparticles
W.J. Youngs, N. Robishaw, M.J. Panzner, K. Hindi, D.A. Medvetz, J. Youngs, C. Tessier, A. Ditto, Y.H. Yun, J. Bauer, D. Lindner
University of Akron, US
Keywords: silver, breast cancer, SCCs, PLGA
Abstract:Our research in cancer focuses on the development of silver carbene complexes (SCCs), for use as antitumor agents. We have found that SCCs have significant activity against a variety of cancers in vitro. Furthermore SCCs are as active as cisplatin against the MB157 (breast) human cancer cell line in vitro and SCCs are 8 times less toxic than cisplatin. Preliminary in vivo studies showed significant tumor regression when the tumor was directly injected with an SCC complex showing that once the drug gets to the target, a result comparable to the in vitro studies is obtained. Two concerns with the systemic use of SCCs are that they degrade in the presence of chloride and also interact with sulfur groups on the proteins in the blood making the delivery of SCCs systemically very difficult. We have addressed the limited stability of SCCs in the bloodstream by encapsulating them in biodegradable poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles. The encapsulation of SCCs in nanoparticles allows for the targeting and localized delivery of the nanoparticles to cancer cells using substituents such as folic acid (Fol) bound to the PEGs on the surface of the nanoparticle. Folic acid receptors are over expressed on cancer cells. Folic acid substituents have been reported to greatly enhance the targeting of nanoparticles for cancer cells. Targeting should result in lower dosages of SCCs and minimize the interactions with healthy mammalian tissue and thereby further lowering the already low toxicity of SCCs relative to the platinum antitumor drugs.