activation of latent hiv using drug-loaded nanoparticles使用药物纳米颗粒激活潜伏的hiv病毒.pdfVIP

Activation of Latent HIV Using Drug-Loaded Nanoparticles 1 2 1,2 Michael Kovochich , Matthew D. Marsden , Jerome A. Zack * 1 Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America, 2 Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America Abstract Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse