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Updated: Feb 7, 2026

Targeting Drugs to Larval Zebrafish Macrophages by Injecting Drug-Loaded Liposomes
Published on: February 18, 2020
Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption
Juan Guan1,2, Qing Shen3, Zui Zhang1,2
1School of Basic Medical Sciences & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200032, China.
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.
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