(603b) Does Co-Encapsulation Matter?: Probing the Biophysical and Functional Impacts of Nanoparticle Combinatorial Delivery

Authors: 
Han, P., Yale University
Fahmy, T., Yale University
Bickerton, S., Yale University
Khan, S., Yale University
Lee, J., Yale University
Song, E., Yale University
Mano, O., Yale University
One clear benefit of using nanoparticles (NPs) for drug delivery and immunotherapy for cancer and autoimmune disorders is the designable, predictable manner of achieving combination delivery. However, an outstanding question is whether multi-payload combination therapy using NPs is best achieved by either a) Separately-encapsulated, or b) Co-encapsulated NPs. We address this question of encapsulation strategies by probing the biophysical implications of delivering differentially-encapsulated NPs, utilizing dye-loaded NPs and in silico modeling of NP uptake. Further, functional and therapeutic impacts were investigated focusing on models of antigen uptake and presentation, employing Separately- or Co- NP systems of antigen delivered with pro- or anti-inflammatory (tolerogenic) adjuvants. In the process of this investigation, we discovered that encapsulation strategies in NPs play a critical role in the spatio-temporal biodistribution kinetics of NPs in target cells and, thus, profoundly influence therapeutic outcomes. Our results provide biophysical and therapeutic insights into the significance of encapsulation strategies that can guide the designs of future NP-mediated combination therapies.