M-C. Daniel Onuta
University of Maryland, Baltimore County,
Keywords: nanoparticles, cancer therapies
Summary:The unique characteristics of inorganic nanoparticles can be exploited for a variety of applications. Here we will discuss the preparation of multifunctional nanoparticles for medical purposes, specifically cancer treatments. Our lab has used a pair of carboxylate- and amine-terminated dendrons to prepare highly stable, zwitterionic gold nanoparticle (AuNP)-based drug delivery platform. These dendronized AuNPs are able to withstand several rounds of lyophilization cycles, are stable in serum, show potential for lysosomal escape, and are nontoxic at concentrations as high as 15 nM. This nanocarrier platform also displays a dense coating, up to 1450 dendrons/NP, which will enable very high payloads. This highly dense and mixed coating on the AuNP will allow for optimum payload of several types of medically relevant entities in a controlled manner. We have also been examining the effect of mild whole-body hyperthermia on the delivery of these AuNP to tumors. The results show an enhanced AuNP delivery (64% increase) to PC3 tumors after 1-hour whole body heating of mice to 40°C. Finally, we are investigating the immune response to these dendronized AuNP for potential use in cancer immunotherapy. The immune response of AuNP-dendron-Fab in comparison to the AuNP-G3CO2H and AuNP-G3NH2 have been assessed via a flow based multiplex bead assay (LuminexTM assay). These studies indicate that the immune responses elicited by AuNPs are concentration-, surface charge- and time-dependent. More studies are ongoing.