Macrophage endocytic trafficking of antiretroviral nanoparticles.
Macrophage endocytic trafficking of antiretroviral nanoparticles.
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DOI：
10.2217/nnm.11.27
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Gendelman HE
中科院分区：
文献类型：
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作者：
Kadiu I;Nowacek A;McMillan J;Gendelman HE
纳米抗逆转录病毒疗法可以提高艾滋病毒感染者的药物依从性。其他益处包括向病毒储库递送特定药物和减少全身毒性。在这篇文章中，我们描述了结晶抗逆转录病毒纳米颗粒（NP）的摄取，细胞内运输和释放在人类单核细胞衍生的巨噬细胞的机制。在网格蛋白依赖性内吞作用之后，NP通过从早期内体分选到再循环内体途径而绕过溶酶体降解。通过siRNA或布雷菲德菌素-A破坏该途径会损害颗粒释放。蛋白质组学和生物学分析表明，颗粒回收主要是Rab 11调节。颗粒被完整释放并保留完整的抗逆转录病毒功效。这些结果表明，抗逆转录病毒纳米制剂的亚细胞转运的可能途径，保持颗粒的完整性和抗逆转录病毒活性，证明这种方法用于靶向药物递送的潜在效用。
Nanoformulated antiretroviral therapy can improve drug compliance for people infected with HIV. Additional benefits would include specific drug deliveries to viral reservoirs and reduction in systemic toxicities. In this article, we describe mechanisms of crystalline antiretroviral nanoparticle (NP) uptake, intracellular trafficking and release in human monocyte-derived macrophages. Following clathrin-dependent endocytosis NPs bypassed lysosomal degradation by sorting from early endosomes to recycling endosome pathways. Disruption of this pathway by siRNAs or brefeldin-A impaired particle release. Proteomic and biological analysis demonstrated that particle recycling was primarily Rab11 regulated. Particles were released intact and retained complete antiretroviral efficacy. These results suggest possible pathways of subcellular transport of antiretroviral nanoformulations that preserve both particle integrity and antiretroviral activities demonstrating the potential utility of this approach for targeted drug delivery.