Enzyme-triggered cargo release from methionine sulfoxide containing copolypeptide vesicles

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Enzyme-responsive drug delivery systems are crucial for targeted cargo release.
• Developing facile and scalable methods for creating such systems remains a challenge.

Purpose of the Study:

• To develop a straightforward and scalable method for preparing enzyme-responsive copolypeptide vesicles.
• To demonstrate the cargo release capabilities of these vesicles triggered by reductase enzymes.

Main Methods:

• Synthesized a diblock copolypeptide precursor, poly(l-methionine)65-b-poly(L-leucine0.5-stat-L-phenylalanine0.5)20.
• Oxidized the precursor in water to form amphiphilic methionine sulfoxide-containing copolypeptides.
• Assembled copolypeptides into vesicles and reduced their size via extrusion.

Main Results:

• Successfully prepared enzyme-responsive copolypeptide vesicles without protecting groups or expensive reagents.
• Vesicles exhibited tunable diameters from micrometers to nanometers.
• Reductase enzyme activity triggered the regeneration of hydrophobic segments, leading to vesicle disruption and cargo release.

Conclusions:

• The developed method offers a facile and scalable approach for creating enzyme-responsive copolypeptide vesicles.
• These vesicles demonstrate potential for controlled cargo delivery applications triggered by specific enzymatic activity.