Modulation of the anti-inflammatory effects of phosphatidylserine-containing liposomes by PEGylation

作者：Quan Hongxuan; Park Hee Chul; Kim Yongjoon; Yang Hyeong Cheol^*

来源：Journal of Biomedical Materials Research Part A, 2017, 105(5): 1479-1486.

DOI：10.1002/jbm.a.35981

• polyethylene glycol
• phosphatidylserine
• liposome
• macrophage
• inflammation

Inhibiting liposome uptake by macrophages using polyethylene glycol (PEG) surface modifications is a widely used approach for extending the half-life of liposomes circulating in the blood. However, the biological effects of PEGylated liposomes on macrophages have not yet been thoroughly investigated. The purpose of this study was to examine the effects of PEGylated phosphatidylserine-containing liposomes (PEG-PSLs) on the expression of two inflammation-associated cytokines, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), in the murine macrophage-like cell line RAW 264.7. Previous studies have demonstrated that PSLs inhibit TNF-alpha secretion and enhance TGF-beta synthesis in macrophages by mimicking apoptotic cells. We found that PEGylation differentially affected the TNF-alpha and TGF-beta levels. The PSL-mediated inhibitory effect on TNF-alpha secretion was enhanced by PEGylation, and PEG-PSLs decreased TGF-beta levels compared with non-PEGylated PSLs. Fluorescence-activated cell sorting analysis demonstrated that 1% PEGylation disturbed the incorporation of PSLs into macrophages. The interference of uptake is thought to extend the binding interaction between PS to PS receptors for PSL-mediated inhibition of TNF-alpha expression. Together, these findings indicate that PEG-PSLs can prevent TNF-alpha secretion without increasing TGF-beta levels in macrophages, and they support the potential clinical use of PEG-PSLs as anti-inflammatory agents with a relatively low potential to induce tissue fibrosis.

• 出版日期2017-5