Elastase activated liposomal delivery to nucleated cells

Area of Science:

• Biotechnology
• Drug Delivery Systems
• Biochemistry

Background:

• Liposomes are versatile drug carriers, but targeted delivery remains a challenge.
• Enzyme-mediated activation of liposomes offers a strategy for triggered release.
• Previous work demonstrated elastase-sensitive peptide-lipids for liposome fusion.

Purpose of the Study:

• To develop and optimize an enzyme-responsive liposome system for targeted delivery.
• To achieve substrate cleavage at physiological elastase levels.
• To demonstrate triggered delivery of encapsulated substances to living cells.

Main Methods:

• Synthesis of a novel elastase-sensitive peptide-lipid (MeO-suc-AAPV-DOPE).
• Co-formulation of the peptide-lipid with a cationic lipid (DODAP).
• Incubation of liposomes with human leukemic (HL60) and endothelial (ECV304) cells in the presence or absence of elastase.
• Assessment of liposome binding, lipid mixing, and cargo delivery (dextrans, calcein).

Main Results:

• The new peptide-lipid showed enhanced sensitivity and selectivity for elastase.
• Elastase-treated liposomes exhibited pH-dependent binding, lipid mixing, and dextran delivery to HL60 cells.
• Enzymatic activity of elastase was confirmed as necessary for activation.
• Activated liposomes successfully delivered encapsulated calcein into ECV304 cell cytoplasm.

Conclusions:

• Enzyme substrate peptides conjugated to fusogenic lipids can trigger specific liposome delivery.
• This approach holds promise for targeted drug delivery to cells expressing specific enzymes.
• The system demonstrates potential for enhanced therapeutic efficacy and reduced off-target effects.