Peptide–MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices. Singha, S., Shao, K., Yang, Y., Clemente-Casares, X., Solé, P., Clemente, A., Blanco, J., Dai, Q., Song, F., Liu, S. W., Yamanouchi, J., Umeshappa, C. S., Nanjundappa, R. H., Detampel, P., Amrein, M., Fandos, C., Tanguay, R., Newbigging, S., Serra, P., Khadra, A., Chan, W. C. W., & Santamaria, P. Nature Nanotech, 12(7):701–710, July, 2017. Bandiera_abtest: a Cg_type: Nature Research Journals Number: 7 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Biotechnology;Nanoparticles Subject_term_id: biotechnology;nanoparticles
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Paper doi abstract bibtex
Paper Paper doi abstract bibtex We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC–NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.
@article{singha_peptidemhc-based_2017,
title = {Peptide–{MHC}-based nanomedicines for autoimmunity function as {T}-cell receptor microclustering devices},
volume = {12},
copyright = {2017 Nature Publishing Group},
issn = {1748-3395},
url = {https://www.nature.com/articles/nnano.2017.56},
doi = {10.1038/nnano.2017.56},
abstract = {We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC–NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.},
language = {en},
number = {7},
urldate = {2021-11-06},
journal = {Nature Nanotech},
author = {Singha, Santiswarup and Shao, Kun and Yang, Yang and Clemente-Casares, Xavier and Solé, Patricia and Clemente, Antonio and Blanco, Jesús and Dai, Qin and Song, Fayi and Liu, Shang Wan and Yamanouchi, Jun and Umeshappa, Channakeshava Sokke and Nanjundappa, Roopa Hebbandi and Detampel, Pascal and Amrein, Matthias and Fandos, César and Tanguay, Robert and Newbigging, Susan and Serra, Pau and Khadra, Anmar and Chan, Warren C. W. and Santamaria, Pere},
month = jul,
year = {2017},
note = {Bandiera\_abtest: a
Cg\_type: Nature Research Journals
Number: 7
Primary\_atype: Research
Publisher: Nature Publishing Group
Subject\_term: Biotechnology;Nanoparticles
Subject\_term\_id: biotechnology;nanoparticles},
keywords = {Biotechnology, Nanoparticles},
pages = {701--710},
file = {Full Text PDF:files/1885/Singha et al. - 2017 - Peptide–MHC-based nanomedicines for autoimmunity f.pdf:application/pdf;Snapshot:files/1887/nnano.2017.html:text/html},
url_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2022/01/Singha-et-al.-2017-Peptide–MHC-based-nanomedicines-for-autoimmunity-f.pdf}
}Downloads: 0
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