Facial Amphiphile-Modified Lipids Highly Sensitize Liposomes toward Secretory Phospholipase A₂

Area of Science:

• Biochemistry
• Materials Science
• Oncology

Background:

• Upregulated secretory phospholipase A2 (sPLA2) in tumors is a target for drug delivery.
• Existing sPLA2-responsive liposomes have limited efficacy and safety concerns due to enzyme hydrolysis and lipid overuse.

Purpose of the Study:

• To introduce a novel membrane-destabilizing mechanism for liposome drug release.
• To engineer liposomes that effectively respond to sPLA2 in tumor microenvironments.

Main Methods:

• Developed liposomes with facial amphiphile (FA)-modified lipids.
• Investigated the SECRIS effect involving lipid extraction, enzymatic cleavage, and FA transition.
• Evaluated drug release, in vitro cytotoxicity, and in vivo antitumor efficacy of oxaliplatin-loaded liposomes.

Main Results:

• The SECRIS effect induced significant payload efflux from liposomes in the presence of sPLA2.
• sPLA2-responsive liposomes demonstrated enhanced drug release and comparable in vitro cytotoxicity.
• Achieved excellent in vivo antitumor efficacy with reduced adverse effects in a mouse model.

Conclusions:

• The SECRIS effect offers a new strategy for designing liposome platforms for sPLA2-positive tumors.
• This approach enhances therapeutic outcomes by improving drug release and reducing toxicity.