Mimicking Apoptosis using Asymmetric Liposomes: A Therapeutic Approach Against Hiv-1 Infection

Macrophages are an important cellular target of HIV-1. Interestingly, they are believed to play also a potential role counteracting the infection. However, HIV-1 is known to impair macrophage's immune functions, such as antibody-mediated phagocytosis.Here, we present liposomes that can bind HIV-1 virus-like particles (HIV-VLPs) while being specifically phagocyted by macrophages. This, in turn, results into co-internalization of HIV-VLPs and their delivery to lysosomes.The investigated liposomes are decorated with anti-Env antibodies and contain phosphatidylserine (PS). PS causes internalization by macrophages (e.g. during apoptosis) via a mechanism supposedly not affected by HIV-1. Hence, PS-liposomes are internalized into the phagocytes due to specific recognition, carrying the previously bound HIV-VLPs.However, if PS were present right away in the outer leaflet of the liposomes, these would be immediately internalized by phagocytes before binding to the virus in the infected organism could be completed. For this reason, we engineered asymmetric vesicles containing PS only in the inner leaflet of the vesicles, where the lipid is “hidden” from macrophages. Spontaneous flipping of PS towards the external milieu is a slow process. During the time required for significant PS exposure (∼several hours), liposomes can bind the virus without being cleared out by the immune system. Eventually, PS becomes fully exposed and the virus-liposome complexes can be internalized by phagocytic cells.With a combination of FACS, spectroscopy, confocal live-cell imaging and electron microscopy we demonstrate that the PS-liposomes presented here are able to elicit efficient HIV-VLPs phagocytosis by macrophages in a time-controlled manner and might represent a new nanotechnological approach to enhance HIV-1 antigen-presentation and reduce ongoing inflammation processes.