Cleavable-Branched Polymer-Modified Liposomes Reduce Accelerated Blood Clearance and Enhance Photothermal Therapy

Abstract

In recent years, cationic liposomes have been successfully used as delivery platforms for mRNA vaccines. Poly­(ethylene glycol) (PEG)-lipid derivatives are widely used to enhance the stability and reduce the toxicity of cationic liposomes. However, these derivatives are often immunogenic, triggering the rise of anti-PEG antibodies. Understanding the role and impact of PEG-lipid derivatives on PEGylated cationic liposomes is key to solving the PEG dilemma. In this study, we designed linear, branched, and cleavable-branched cationic liposomes modified with PEG-lipid derivatives and investigated the effect of the liposome-induced accelerated blood clearance (ABC) phenomenon on photothermal therapy. Our study indicated that the linear PEG-lipid derivatives mediated the effect of photothermal therapy by stimulating splenic marginal zone (MZ) B cells to secrete anti-PEG antibodies and increasing the level of IgM expression in the follicular region of the spleen. However, the cleavable-branched and branched PEG-lipid derivatives did not activate the complement system and avoided the ABC phenomenon by inducing noticeably lower levels of anti-PEG antibodies. The cleavable-branched PEGylated cationic liposomes improved the effect of photothermal therapy by reversing the charge on the liposome surface. This detailed study of PEG-lipid derivatives contributes to the further development and clinical application of PEGylated cationic liposomes.

GSH-Responsive Liposomes with Heat Shock Protein Regulatory Ability for Efficient Photodynamic/Photothermal Combined Therapy of Tumors

“…It has been found that tumor cells are rich in vascular structure, and their endothelial interstitial space is sparse and incomplete; thus, macromolecules and lipids are able to selectively pass through and stay in the tumor cells. − Therefore, if the selectivity of AIE materials is improved through the use of nanocarrier technology, so that the AIE materials are more aggregated in the tumor cells and the drug concentration in the tumor is increased, the enhanced antitumor therapy can be better achieved. Liposome is a spherical bilayer vesicle structure, whose phospholipid bilayer has an outer surface layer formed by a hydrophilic head and a hydrophobic tail in the middle part of the membrane; due to this special structure, the liposome is therefore capable of carrying not only hydrophilic substances but also hydrophobic substances. − In practical applications, a variety of smart-responsive nanocarriers can be prepared by combining stimulus-responsive factors (e.g., pH, temperature, enzymes, etc.) with liposomes.…”