Microglia-targeting nanotherapeutics for neurodegenerative diseases
Microglia-targeting nanotherapeutics for neurodegenerative diseases
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DOI：
10.1063/5.0013178
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发表时间：
2020-09
影响因子：
6
通讯作者：
Nanxia Zhao;Nicola L Francis;Hannah R. Calvelli;P. Moghe
中科院分区：
文献类型：
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作者：
Nanxia Zhao;Nicola L Francis;Hannah R. Calvelli;P. Moghe
纳米技术的进步使得纳米治疗平台的设计成为可能，该平台可以解决向中枢神经系统（CNS）靶向输送活性治疗剂的挑战。虽然之前关于中枢神经系统纳米治疗的大多数研究都集中在神经元和内皮细胞上，但中枢神经系统的主要常驻免疫细胞小胶质细胞也正在成为神经退行性变的有希望的细胞靶标，因为它们在神经炎症中发挥着重要作用。在正常生理条件下，小胶质细胞通过清除病理因子来保护神经元。然而，小胶质细胞长期暴露于兴奋剂会引起持续激活，并因促炎剂的释放而导致神经元损伤，导致神经炎症和神经退行性变。本观点强调了设计用于治疗神经退行性疾病的小胶质细胞靶向纳米疗法时应考虑的标准。这些标准包括将特定的小胶质细胞受体靶向配体或肽缀合到纳米颗粒表面以实现靶向递送，利用小胶质细胞吞噬特性，以及利用具有低免疫反应性和神经毒性的生物相容性和可生物降解的纳米材料。此外，用于受控抑制有毒蛋白质聚集和调节小胶质细胞活化途径的某些治疗剂也可以掺入纳米颗粒结构内，而不损害稳定性。总体而言，考虑到神经退行性疾病的多方面疾病机制，针对小胶质细胞的纳米药物和纳米治疗颗粒可能有潜力解决该疾病的多种病理决定因素，并引导小胶质细胞表型谱向更具神经保护性的状态转变。
Advances in nanotechnology have enabled the design of nanotherapeutic platforms that could address the challenges of targeted delivery of active therapeutic agents to the central nervous system (CNS). While the majority of previous research studies on CNS nanotherapeutics have focused on neurons and endothelial cells, the predominant resident immune cells of the CNS, microglia, are also emerging as a promising cellular target for neurodegeneration considering their prominent role in neuroinflammation. Under normal physiological conditions, microglia protect neurons by removing pathological agents. However, long-term exposure of microglia to stimulants will cause sustained activation and lead to neuronal damage due to the release of pro-inflammatory agents, resulting in neuroinflammation and neurodegeneration. This Perspective highlights criteria to be considered when designing microglia-targeting nanotherapeutics for the treatment of neurodegenerative disorders. These criteria include conjugating specific microglial receptor-targeting ligands or peptides to the nanoparticle surface to achieve targeted delivery, leveraging microglial phagocytic properties, and utilizing biocompatible and biodegradable nanomaterials with low immune reactivity and neurotoxicity. In addition, certain therapeutic agents for the controlled inhibition of toxic protein aggregation and for modulation of microglial activation pathways can also be incorporated within the nanoparticle structure without compromising stability. Overall, considering the multifaceted disease mechanisms of neurodegeneration, microglia-targeted nanodrugs and nanotherapeutic particles may have the potential to resolve multiple pathological determinants of the disease and to guide a shift in the microglial phenotype spectrum toward a more neuroprotective state.