Multiple Drug Delivery with Layer-by-Layer Nanoparticles
Given the multifactoral challenges presented by ovarian cancer, it is essential that future treatments attack tumors by targeting a variety of rationally chosen biological weaknesses. This strategy will likely lead to enhanced cell-killing by cutting off auxiliary survival pathways that cancer cells can leverage. By simultaneously attacking multiple biological pathways, combination therapies show promise at reducing the incidence of drug-resistance, which is a major cause of morbidity for ovarian cancer patients in particular. The layered architecture of our nanoparticles allows for distinct drug payloads to be incorporated within a specific layer, allowing us to control composition on the nanoscale. This control provides an unprecedented advantage in terms of designing nanoparticles that carry combinations of drugs. Utilizing layer-by-layer techniques, we are able to deliver drugs that would otherwise interfere with one another if co-encapsulated within a traditional nanoparticle. Examples of this include DNA-damaging agents, like cisplatin, bundled with gene therapies, like small interfering RNAs. These constituents would react with one another if co-localized, but in our systems the drugs are spatially segregated from one another while still being part of a contiguous particle. I focus on discovering particularly synergistic combinations of gene therapy with traditional chemotherapy for ovarian cancer. By directly targeting the DNA damage pathways that cancer cells use to evade, and ultimately resist, the effects of chemotherapeutics, I hope to develop nanoparticles that can significantly reduce the ability for ovarian cancers to develop platinum-resistance.