title: Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.
abstract: Next-generation nanoparticle-based drug delivery systems require the ability to target specific organelles or subcellular regions in selected target cells. Human immunodeficiency virus type I (HIV-1) particles are evolutionarily optimized nanocarriers that have evolved to avoid intracellular degradation and achieve enrichment at the synapse between mature dendritic cells (mDCs) and T cells by subverting cellular trafficking mechanisms. This study demonstrates that integration of the glycosphingolipid, GM3, in a membrane around a solid nanoparticle (NP) core is sufficient to recapitulate key aspects of the virus particle trafficking in mDCs. GM3-presenting artificial virus NPs (GM3-AVNs) accumulate in CD169(+) and CD81(+) nonlysosomal compartments in an actin-dependent process that mimics the sequestration of HIV-1. Live-cell optical tracking studies reveal a preferential recruitment and arrest of surface scanning CD4(+) T cells in direct vicinity to the AVN-enriched compartments. The formed mDC-T cell conjugates exhibit strong morphological similarities between the GM3-AVN-containing mDC-T cell synapse and the HIV-1 virological synapse, indicating that GM3-CD169 interactions alone are sufficient for establishing the mDC-T cell virological synapse. These results emphasize the potential of the GM3-AVN approach for providing therapeutic access to a key step of the host immune response--formation of the synaptic junction between an antigen-presenting cell (mDC) and T cells--for modulating and controlling immune responses.
authors: †Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, United States.
authors: Xinwei
authors: X
authors: Yu
authors: †Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, United States.
authors: Fangda
authors: F
authors: Xu
authors: ‡Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, United States.
authors: Nora-Guadalupe P
authors: NG
authors: Ramirez
authors: ‡Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, United States.
authors: Suzanne D G
authors: SD
authors: Kijewski
authors: ‡Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, United States.
authors: Hisashi
authors: H
authors: Akiyama
authors: ‡Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, United States.
authors: Suryaram
authors: S
authors: Gummuluru
authors: †Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, United States.
authors: Björn M
authors: BM
authors: Reinhard
mesh_terms: D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D005679:G(M3) Ganglioside / Q000378:metabolism; D006046:Gold / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects*; D053768:Metal Nanoparticles; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014771:Virion / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D005679:G(M3) Ganglioside; D063267:Sialic Acid Binding Ig-like Lectin 1; D006046:Gold
keywords: GM3; Siglec1; biomimetics; drug delivery; glycosphingolipid; human immunodeficiency virus; stealth nanoparticles