Biodegradable block copolymer micelles with thiol-responsive sheddable coronas

Area of Science:

• Polymer Chemistry
• Materials Science
• Nanotechnology

Background:

• Biodegradable polymers like polylactide (PLA) are crucial for drug delivery.
• Developing stimuli-responsive drug delivery systems enhances therapeutic efficacy.
• Micellar nanoparticles offer a versatile platform for encapsulating and delivering therapeutic agents.

Purpose of the Study:

• To synthesize novel sheddable micelles with biodegradable PLA cores.
• To engineer micelles that release their hydrophilic corona in response to thiol stimuli.
• To evaluate the biocompatibility and potential biomedical applications of these novel micelles.

Main Methods:

• Synthesis of PLA-based amphiphilic block copolymers using ring-opening polymerization and atom transfer radical polymerization.
• Functionalization of block copolymers with disulfide linkages at block junctions.
• Aqueous micellization to form core/shell micelles and investigation of thiol-responsive degradation.
• Characterization using NMR and GPC to confirm polymer structure and control.

Main Results:

• Well-defined PLA-based block copolymers were successfully synthesized with controlled molecular weights (Mw/Mn < 1.2).
• Aqueous micellization formed core/shell structures with disulfide bonds at the core-corona interface.
• Exposure to thiols induced cleavage of disulfide bonds, leading to corona shedding and PLA core precipitation.
• The prepared sheddable micelles demonstrated no cytotoxicity, indicating good biocompatibility.

Conclusions:

• Novel sheddable micelles with biodegradable PLA cores and thiol-cleavable disulfide linkages were successfully prepared.
• These micelles exhibit controlled release of hydrophilic coronas triggered by thiols, leading to destabilization of PLA cores.
• The non-cytotoxic nature of these micelles suggests their potential utility in biomedical applications, such as targeted drug delivery.