Alteration of Nanoparticle Pharmacokinetics By Tumor-Induced Modulation of the Immune Response

Circulation persistence has been established as a key characteristic of nanoparticles for passively targeting tumors, an important facet of chemotherapeutic delivery. However, many drugs are hindered by toxicity issues. Notably, Cisplatin—approved for use in a wide variety of cancers—has significant renal and neurological toxicities. Incorporating the drug into a nanoparticle increases tumor accumulation while simultaneously reducing side effects caused by systemic exposure.

We have formulated and optimized PEGylated, polymeric hydrogels using the PRINT platform, and complexed cisplatin into the particles. The maximum tolerated dose of the particles is being determined and compared to free drug. Cytotoxicity in several lung carcinoma lines is being investigated, and efficacy studies in mice will be carried out in both subcutaneous and orthotopic non-small cell lung xenografts (A549). Renal toxicity and neuropathy will also be assayed. We anticipate reduced side effects and higher survival probability compared to the current standard of care.