Issue 14, 2022

Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins

Abstract

Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC–lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC–lipids with polymerization degrees of 10 (MPC10–lipid), 20 (MPC20–lipid), 50 (MPC50–lipid), and 100 (MPC100–lipid), and coated liposomes with 1, 5, or 10 mol% PMPC–lipids (PMPC–liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N′,N′-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC–lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1–10 mol%). Apolipoprotein A-I is detected on PMPC–liposomes with a higher molecular weight and higher molar ratio of PMPC–lipids, whereas α2-macroglobulin is detected on non-modified, PEGylated, and PMPC–liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10–lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20–lipid and 5 mol% and 10 mol% MPC50–lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC–lipids can be a possible strategy for avoiding complement activation.

Graphical abstract: Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins

Supplementary files

Article information

Article type
Paper
Submitted
06 Jūl. 2021
Accepted
18 Sept. 2021
First published
20 Sept. 2021

J. Mater. Chem. B, 2022,10, 2512-2522

Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins

A. Adler, Y. Inoue, K. N. Ekdahl, T. Baba, K. Ishihara, B. Nilsson and Y. Teramura, J. Mater. Chem. B, 2022, 10, 2512 DOI: 10.1039/D1TB01485D

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