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Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption

Targeting ligands are anticipated to facilitate the precise delivery of therapeutic agents to diseased tissues; however, they may also severely affect the interaction of nanocarriers with plasma proteins. Here, we study the immunocompatibility of brain-targeted liposomes, which inversely correlates...

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Autores principales: Guan, Juan, Shen, Qing, Zhang, Zui, Jiang, Zhuxuan, Yang, Yang, Lou, Meiqing, Qian, Jun, Lu, Weiyue, Zhan, Changyou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065320/
https://www.ncbi.nlm.nih.gov/pubmed/30061672
http://dx.doi.org/10.1038/s41467-018-05384-1
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author Guan, Juan
Shen, Qing
Zhang, Zui
Jiang, Zhuxuan
Yang, Yang
Lou, Meiqing
Qian, Jun
Lu, Weiyue
Zhan, Changyou
author_facet Guan, Juan
Shen, Qing
Zhang, Zui
Jiang, Zhuxuan
Yang, Yang
Lou, Meiqing
Qian, Jun
Lu, Weiyue
Zhan, Changyou
author_sort Guan, Juan
collection PubMed
description Targeting ligands are anticipated to facilitate the precise delivery of therapeutic agents to diseased tissues; however, they may also severely affect the interaction of nanocarriers with plasma proteins. Here, we study the immunocompatibility of brain-targeted liposomes, which inversely correlates with absorbed natural IgM. Modification of long, stable positively charged peptide ligands on liposomes is inclined to absorb natural IgM, leading to rapid clearance and enhanced immunogenicity. Small peptidomimetic D8 developed by computer-aided peptide design exhibits improved immunocompatibility by attenuating natural IgM absorption. The present study highlights the effects of peptide ligands on the formed protein corona and in vivo fate of liposomes. Stable positively charged peptide ligands play double-edged roles in targeted delivery, preserving in vivo bioactivities for binding receptors and long-term unfavorable interactions with the innate immune system. The development of D8 provides insights into how to rationally design immunocompatible drug delivery systems by modulating the protein corona composition.
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spelling pubmed-60653202018-07-31 Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption Guan, Juan Shen, Qing Zhang, Zui Jiang, Zhuxuan Yang, Yang Lou, Meiqing Qian, Jun Lu, Weiyue Zhan, Changyou Nat Commun Article Targeting ligands are anticipated to facilitate the precise delivery of therapeutic agents to diseased tissues; however, they may also severely affect the interaction of nanocarriers with plasma proteins. Here, we study the immunocompatibility of brain-targeted liposomes, which inversely correlates with absorbed natural IgM. Modification of long, stable positively charged peptide ligands on liposomes is inclined to absorb natural IgM, leading to rapid clearance and enhanced immunogenicity. Small peptidomimetic D8 developed by computer-aided peptide design exhibits improved immunocompatibility by attenuating natural IgM absorption. The present study highlights the effects of peptide ligands on the formed protein corona and in vivo fate of liposomes. Stable positively charged peptide ligands play double-edged roles in targeted delivery, preserving in vivo bioactivities for binding receptors and long-term unfavorable interactions with the innate immune system. The development of D8 provides insights into how to rationally design immunocompatible drug delivery systems by modulating the protein corona composition. Nature Publishing Group UK 2018-07-30 /pmc/articles/PMC6065320/ /pubmed/30061672 http://dx.doi.org/10.1038/s41467-018-05384-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Guan, Juan
Shen, Qing
Zhang, Zui
Jiang, Zhuxuan
Yang, Yang
Lou, Meiqing
Qian, Jun
Lu, Weiyue
Zhan, Changyou
Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption
title Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption
title_full Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption
title_fullStr Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption
title_full_unstemmed Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption
title_short Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption
title_sort enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural igm absorption
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065320/
https://www.ncbi.nlm.nih.gov/pubmed/30061672
http://dx.doi.org/10.1038/s41467-018-05384-1
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