Nanomedicine: Nanotechnology, Biology and Medicine
Original ArticleTime-controlled phagocytosis of asymmetric liposomes: Application to phosphatidylserine immunoliposomes binding HIV-1 virus-like particles
Graphical Abstract
We present a novel asymmetric immunoliposomal system that is able to bind a surface protein of HIV-1. The structural lipid asymmetry (i.e., the lipid phosphatidylserine confined to the inner leaflet) allows the evasion of the immune system long enough to locate and bind the pathogen of interest. After a certain amount of time (e.g., 24 hours), phosphatidylserine will be exposed in the outer leaflet and trigger internalization and disposal of the liposome–pathogen complex by macrophages.
Section snippets
Methods
See Supplementary Materials.
Fast internalization of symmetric immunoliposomes hinders binding to VLPs
We have previously shown that αEnv-PS-LUVs can bind Env proteins on the VLPs surface and, due to the presence of PS, are promptly phagocytosed by macrophages, together with the bound VLPs.7 Due to the strong interaction between PS-LUVs and macrophages, in our previous work, we let αEnv-PS-LUVs interact with VLPs before the actual measurements. This expedient allowed the binding between liposomes and VLPs to take place in the absence of macrophages, in order to simplify the interpretation of the
Discussion
We have recently described PS-containing LUVs decorated with αEnv antibodies as an approach that could be used to elicit HIV-1 phagocytosis by macrophages in vivo.7 αEnv-PS-LUVs are recognized as apoptotic cells due to the presence of PS8 and are efficiently internalized by macrophages together with previously bound viral particles.7
PS-LUVs (30 mol% PS) are internalized as much as 10 times more efficiently than those without PS.7 This observation suggested a specific recognition of PS by
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2022, HeliyonCitation Excerpt :A number of surface-functionalized liposomal carrier systems, known as immunoliposomes, have been shown to navigate themselves to pathological cells due to the specific interaction among antibodies that has been attached to the surface of the liposomes and antigen epitopes or small particles that are displayed by the targeted pathogenic cells. Such types of immuneliposomal carriers having the tendency to mimicking the apoptotic cells as a result efficiently internalized by macrophages [227, 228, 229, 230]. For example, recombinant B subunit of cholera toxin (rCTB) was covalently coupled to the outer surface of the small unilamellar liposomes for targeted delivery of encapsulated saliva-binding region (SBR) of Streptococcus mutans antigen I/II (AgI/II) protein to Peyer's patches (aggregated lymphoid nodules) and enhanced the secretory IgA responses in mice.
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2020, Advanced Drug Delivery ReviewsCitation Excerpt :In addition, Woll et al. reported a chemoenzymatic method based on Sortase-A mediated transpeptidation [53]. Non-covalent attachments based on biotin and avidin interactions [54–57] or through a bispecific PEG-engager [58] were also listed. There have been only a few studies that compared the different conjugated structures.
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Enhancement of macrophage uptake via phosphatidylserine-coated acetalated dextran nanoparticles
2019, Journal of Drug Delivery Science and TechnologyCitation Excerpt :The presence of DPPS on the cellular surface is known to cause an “eat-me” signal in cells that are transitioning toward an apoptotic state, causing macrophages to identify and phagocytose the dying cells [1–3,7,11]. Therefore, in terms of recognition, the DPPS coating on the Ac-Dex NP was identified by the macrophages, which produced the necessary phagocytotic action, resulting in cellular uptake of the particles [1,6,7,16,25,27]. In most cases, apoptosis is initiated by the presence DPPS and other signaling pathways such as receptor-ligand interactions or identification of PS binding proteins produced by phagocytes.
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2018, Nanostructures for the Engineering of Cells, Tissues and Organs: From Design to ApplicationsImmunoliposomes: A review on functionalization strategies and targets for drug delivery
2017, Colloids and Surfaces B: BiointerfacesCitation Excerpt :Also, liposomes bearing Fab’ portions were 2.3-fold less immunogenic than liposomes bearing the entire IgG [58]. In another approach, phosphatidylserine immunoliposomes targeted with antibodies that bind HIV-1 virus-like particles were initially protected from macrophage uptake, in order to provide enough time to circulate through the body and achieve maximum virus binding [128]. Moreover, anti-CD4 conjugated immunoliposomes containing 2 antiretroviral drugs (nevirapine and saquinavir) inhibited viral proliferation at a lower concentration than free drugs [41].
S.C. is financed by DFG Grant CH1238/3-1.
The authors declare no competing financial interests.
An abstract regarding some of the results described in the manuscript was presented at the Biophysical Society Meeting 2014.