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

Juan Guan, Qing Shen, Zui Zhang, Zhuxuan Jiang, Yang Yang, Meiqing Lou, Jun Qian, Weiyue Lu and Changyou Zhan ()
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Juan Guan: Fudan University
Qing Shen: Shanghai Jiao Tong University
Zui Zhang: Fudan University
Zhuxuan Jiang: Fudan University
Yang Yang: Fudan University
Meiqing Lou: Shanghai Jiaotong University
Jun Qian: Ministry of Education
Weiyue Lu: Ministry of Education
Changyou Zhan: Fudan University

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05384-1

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