Enhanced treatment of breast cancer via biodegradable polymer nanoparticles

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

ABSTRACT Breast cancer remains the second largest cause of cancer related deaths in the USA. Heat shock protein (HSP) inhibition has emerged as a promising target to treat breast cancer. However, the drawback of these drugs is cardiotoxicity. Nanoparticle delivery of HSP inhibitors should avoid this side-effect, as well as increasing delivery of drug to the tumor. Various types of nanoparticles can also enhance the effects of photothermal therapy on cancer killing. Moreover, photothermal therapy together with delivery of HSP inhibitors is a potent combination treatment. However, many of the types of nanoparticles typically used in photothermal therapy are not well-suited for drug delivery, are very slowly excreted, are expensive, are challenging to scale up and are synthesized using toxic reagents or organic solvents. We herein propose a novel polyphosphazene nanoparticle (PPNP) to treat breast cancer via enhancing photothermal therapy and delivering a HSP inhibitor. The PPNP will be also loaded with ultrasmall silver sulfide nanoparticles that provide strong photothermal therapy enhancement, but when released from the biodegradable nanoparticle, are rapidly renally cleared. The silver sulfide nanoparticles also provide contrast for multiple imaging techniques (i.e. computed tomography, mammography, photoacoustics and fluorescence), thereby allowing delivery to be assessed and guiding laser irradiation. This is a low cost platform that is synthesized by microfluidics, which enables large scale synthesis of a homogenous product. These PPNP will be synthesized, characterized, and tested for their contrast production. Drug loading and release will be assessed, as will their enhancement of photothermal heating. Breast cancer killing will be studied in vitro and in vivo. We will also perform in vivo imaging, as well as safety and clearance studies. Overall, we expect to develop a potent new tool for the treatment of breast cancer.