Non-affinity factors modulating vascular targeting of nano- and microcarriers.
Non-affinity factors modulating vascular targeting of nano- and microcarriers.
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DOI：
10.1016/j.addr.2015.10.011
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发表时间：
2016-04-01
影响因子：
16.1
通讯作者：
Muzykantov VR
中科院分区：
文献类型：
--
作者：
Myerson JW;Anselmo AC;Liu Y;Mitragotri S;Eckmann DM;Muzykantov VR
能够归巢并粘附到特定血管生物标志物的颗粒有潜力作为药物递送的基本工具，用于调节多种病理学，包括炎症、血栓形成和肺部疾病。颗粒表面上亲和配体的呈现提供了一种将颗粒靶向治疗感兴趣位点的方法，但在确定颗粒的靶向能力时还有许多其他因素发挥作用。本综述总结了纳米和微粒设计中的几个关键考虑因素，这些设计可调节靶向递送而不直接改变表位特异性亲和力。也就是说，我们描述了基础载体定义中的因素（包括形状、大小和灵活性）对载体进入、粘附和整合目标生物环境的能力的影响。此外，我们总结了循环中载体行为的基本动力学，考虑到与循环中细胞的相互作用以及血流动力学在介导载体到目标位点的方向中的作用。最后，我们注意到靶细胞中载体的摄取和细胞内运输的非亲和力方面。总而言之，这里提出的最新研究结果可能提供一个机会，利用配体靶向载体行为中的缓解因素来优化靶向。
Particles capable of homing and adhering to specific vascular biomarkers have potential as fundamental tools in drug delivery for mediation of a wide variety of pathologies, including inflammation, thrombosis, and pulmonary disorders. The presentation of affinity ligands on the surface of a particle provides a means of targeting the particle to sites of therapeutic interest, but a host of other factors come into play in determining the targeting capacity of the particle. This review presents a summary of several key considerations in nano- and microparticle design that modulate targeted delivery without directly altering epitope-specific affinity. Namely, we describe the effect of factors in definition of the base carrier (including shape, size, and flexibility) on the capacity of carriers to access, adhere to, and integrate in target biological milieus. Furthermore, we present a summary of fundamental dynamics of carrier behavior in circulation, taking into account interactions with cells in circulation and the role of hemodynamics in mediating the direction of carriers to target sites. Finally, we note non-affinity aspects to uptake and intracellular trafficking of carriers in target cells. In total, recent findings presented here may offer an opportunity to capitalize on mitigating factors in the behavior of ligand-targeted carriers in order to optimize targeting.