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.