Targeted Delivery of Anti-inflammatory and Imaging Agents to Microglial Cells with Polymeric Nanoparticles.
Insult to the central nervous system (CNS) results in an early inflammatory response, which can be exploited as an initial indicator of neurological dysfunction. Nanoparticle drug delivery systems provide a mechanism to increase the uptake of drugs into specific cell types in the CNS such as microglia, the resident macrophage responsible for innate immune response. In this study, we developed two nanoparticle-based carriers as potential theranostic systems for drug delivery to microglial cells. Poly(lactic-co-glycolic) acid (PLGA)- and l-tyrosine polyphosphate (LTP)-based nanoparticles were synthesized to encapsulate the magnetic resonance imaging (MRI) contrast agent, gadolinium-diethylenetriaminepentaacetic acid (Gd[DTPA]), or the anti-inflammatory drug, rolipram. Robust uptake of both polymer formulations by microglial cells was observed with no evidence of toxicity. In mixed glial cultures, we observed a preferential internalization of nanoparticles by microglia compared to that of astrocytes. Moreover, exposure of our nanoparticles to microglial cells did not induce the release of the proinflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-1 β (IL-1β), or interleukin-6 (IL-6). These studies provide a foundation for the development of LTP nanoparticles as a platform for the delivery of imaging agents and drugs to the sites of neuroinflammation.
['Cahalane|Celina|C|0000-0001-6722-6977', 'Bonezzi|Jason|J|', 'Shelestak|John|J|', 'Clements|Robert|R|', 'Boika|Aliaksei|A|0000-0001-8249-0741', 'Yun|Yang H|YH|0000-0001-5447-8833', 'Shriver|Leah P|LP|']
D000818:Animals D000893:Anti-Inflammatory Agents D002460:Cell Line D005455:Fluorescent Antibody Technique D008279:Magnetic Resonance Imaging D055432:Metabolomics D051379:Mice D017628:Microglia D018613:Microscopy, Confocal D053758:Nanoparticles D010755:Organophosphates D011108:Polymers
nanoparticles microglia theranostic l-tyrosine polyphosphate