T-Cell-Mimicking Nanoparticles Can Neutralize HIV Infectivity

Abstract

To improve human immunodeficiency virus (HIV) treatment and prevention, therapeutic strategies that can provide effective and broad-spectrum neutralization against viral infection are highly desirable. Inspired by recent advances of cell-membrane coating technology, herein, plasma membranes of CD4⁺ T cells are collected and coated onto polymeric cores. The resulting T-cell-membrane-coated nanoparticles (denoted as "TNPs") inherit T cell surface antigens critical for HIV binding, such as CD4 receptor and CCR5 or CXCR4 coreceptors. The TNPs act as decoys for viral attack and neutralize HIV by diverting the viruses away from their intended host targets. This decoy strategy, which simulates host cell functions for viral neutralization rather than directly suppressing viral replication machinery, has the potential to overcome HIV genetic diversity while not eliciting high selective pressure. In this study, it is demonstrated that TNPs selectively bind with gp120, a key envelope glycoprotein of HIV, and inhibit gp120-induced killing of bystander CD4⁺ T cells. Furthermore, when added to HIV viruses, TNPs effectively neutralize the viral infection of peripheral mononuclear blood cells and human-monocyte-derived macrophages in a dose-dependent manner. Overall, by leveraging natural T cell functions, TNPs show great potential as a new therapeutic agent against HIV infection.

Keywords: HIV; T cell; antiretroviral therapy; biomimetic nanoparticle; cell membrane coating; viral neutralization.