(497d) Highly Tunable Fluorescent Nanoparticle Library for Optimizing Neuronal Drug Delivery

Nanomedicine is a promising avenue for neuronal drug delivery, due to 1) favorable pharmacokinetics of encapsulated drugs, and 2) the potential for targeting of specific tissue and cell types. However, in order to optimize these nanotherapeutic systems, nanoparticle-neuron interplay needs to be fully characterized. Previous studies have indicated that size and surface properties, such as charge and functionalization, play an important role in nanoparticle uptake by different cell populations. However, robust studies of these interactions in neurons remain to be seen. In order to address this gap, we have developed a novel, tunable nanoprobe that allows for the characterization of uptake kinetics while recapitulating the characteristics of drug-loaded nanoparticles.

In this study, a quantum-dot nanoparticle (qNP) library was assembled by encapsulating CdSe-based quantum dots into polymeric nanoparticles using Flash Nanoprecipitation (FNP). Size and surface characteristics were tuned respectively by varying the ratio of core to stabilizing polymer and altering stabilizing polymer chemistry. Spatiotemporal qNP uptake was examined in vitro and in vivo. The resulting library of qNP probes demonstrated tunability in size (50-250 nm diameter) and surface charge (-30 to 0mV). In vitro studies showed size-dependent uptake kinetics of PEGylated qNPs into Schwann cells and colocalization with endosomes. In dorsal root ganglia, particles were visualized in both soma and neurites. In vivo studies show that qNPs were taken up by mouse intestinal epithelium and enteric nerves.

In conclusion, we demonstrate the versatility of FNP as a scalable single-step process for formulating nanocarriers, and begin to elucidate the assembly mechanics of the novel polymer-nanocrystal composites. Preliminary biological studies confirm the promise of polymer nanoparticles to act as delivery systems to nerves via intrathecal and rectal delivery. Additionally, we present foundational work elucidating the relationship between nanoparticle size, surface charge, and neuronal internalization efficiency. Overall, the qNP library is a novel tool that can be used for optimizing drug delivery systems and studying nano-bio interactions in any tissue system.