pNIPAm particles for protein delivery to tumor-associated macrophages.

Abstract

<p>Drug delivery vehicles are designed to address limitations associated with traditional drug administration methods. In the case of cancer immunotherapy, the problem often lies in toxicity of drug, local delivery and short residence time in the body. In cancer, macrophages are prime targets for immunotherapy. They exist on a spectrum of phenotypes, with M1 classically activated and M2 alternatively activated macrophages being the traditional ends of this spectrum. M2 macrophages are pro-wound healing, and M1 macrophages are pro-inflammatory. Tumor associated macrophages (TAM’s) are mostly M2-like macrophages and promote tumor growth. Interleukin 12 (IL-12) delivery to macrophages has been shown to reprogram M2 macrophages to M1 macrophages. Poly(N-isopropylacrylamide)-co-acrylic acid-co-poly(ethyleneglycol) diacrylate (pNIPAm-co-PEGDA Microgel) particles have attractive properties for drug delivery for IL-12. The cytotoxicity, degradative properties, particle internalization and doxorubicin release was studied using these particles. Viability of polarized macrophages in the presence of these particles was found to be above 70% at 0.0125 mg/mL. Doxorubicin release studies showed release occurred over 14 days. Internalization of particles was imaged using fluorescein-loaded particles. Future work will include model protein release studies and further particle characterization. Results from this work will be applied to drug delivery design and further work into macrophage reprogramming.</p>