Dual enzyme responsive mannose-6-phosphate based vesicle for controlled lysosomal delivery

Area of Science:

• Biomaterials Science
• Cell Biology
• Drug Delivery Systems

Background:

• Lysosomal delivery is crucial for various cellular processes and therapeutic strategies.
• Developing targeted delivery systems that respond to specific cellular environments remains a challenge.

Purpose of the Study:

• To engineer stable, biomimetic vesicles capable of dual-cargo encapsulation and lysosomal targeting.
• To investigate the enzyme-responsive properties of mannose-6-phosphate (M6P) lipid assemblies for controlled cargo release.

Main Methods:

• Synthesis of mannose-6-phosphate (M6P) lipid-based vesicles.
• Encapsulation of dual cargo (dye/drug and protein/enzyme).
• In vitro assessment of lysosomal targeting and cargo delivery in HEK-293 cells.
• Evaluation of enzyme-responsive morphology changes and cargo release kinetics.

Main Results:

• The M6P lipid vesicles successfully encapsulated and delivered both small molecule (dye/drug) and large molecule (protein/enzyme) cargo.
• Exclusive targeting and delivery to the lysosome were confirmed in HEK-293 cells.
• Enzyme-responsive changes in vesicle morphology were observed, leading to temporally controlled cargo release.

Conclusions:

• Mannose-6-phosphate lipid vesicles represent a promising platform for dual-cargo delivery to lysosomes.
• The enzyme-responsive nature of these vesicles allows for tunable and controlled release of therapeutic payloads.
• This approach has potential applications in lysosomal storage disorder treatments and other cellular therapies.