Targeted Delivery of Anti-inflammatory and Imaging Agents to Microglial Cells with Polymeric Nanoparticles
Targeted Delivery of Anti-inflammatory and Imaging Agents to Microglial Cells with Polymeric Nanoparticles
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DOI：
10.1021/acs.molpharmaceut.9b00489
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发表时间：
2020-06-01
影响因子：
4.9
通讯作者：
Shriver, Leah P.
中科院分区：
文献类型：
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作者：
Cahalane, Celina;Bonezzi, Jason;Shriver, Leah P.
对中枢神经系统(CNS)的侮辱会导致早期的炎症反应，这可以作为神经功能障碍的初步指标。纳米粒给药系统提供了一种机制，可以增加药物对中枢神经系统特定细胞类型的摄取，如负责先天性免疫反应的常驻巨噬细胞小胶质细胞。在这项研究中，我们开发了两种基于纳米颗粒的载体，作为潜在的治疗系统，将药物输送到小胶质细胞。合成了基于聚乳酸-羟基乙酸和L-酪氨酸聚磷酸的纳米粒子，并将其包裹在磁共振造影剂Gd[DTPA]或抗炎药罗利普兰中。观察到小胶质细胞对这两种聚合物制剂的强劲摄取，没有毒性的证据。在混合胶质细胞培养中，我们观察到与星形胶质细胞相比，小胶质细胞优先内化纳米颗粒。此外，将我们的纳米颗粒暴露在小胶质细胞中并没有诱导促炎细胞因子肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)或白介素6(IL-6)的释放。这些研究为开发LTP纳米颗粒作为向神经炎症部位输送显像剂和药物的平台提供了基础。
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 alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), 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.