Synthesis and Acidic pH-Responsive Disassembly of Dual-Location Shell-Sheddable/Core-Degradable Block Copolymer...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Amphiphilic block copolymers (ABPs) and their nanoassemblies are crucial for tumor-targeted drug delivery.
• Current designs with single-location acid-labile groups limit controlled degradation and therapeutic release.
• Inefficient drug release from nanoassemblies hinders effective cancer therapy.

Purpose of the Study:

• To develop a novel dual-location acidic pH-responsive degradation strategy for ABPs nanoassemblies.
• To achieve controlled and synergistically enhanced release of encapsulated therapeutics.
• To enhance tumor-targeting drug delivery and cancer therapy efficacy.

Main Methods:

• Synthesized well-defined ABPs with two different acid-labile linkages (benzaldehyde acetal and benzoic imine) using reversible deactivation radical polymerization.
• Formed colloidally stable nanoassemblies via aqueous micellization.
• Evaluated pH-responsive degradation at physiological (pH 7.3), tumoral (pH 6.5), and endo/lysosomal (pH 5.0) conditions.
• Loaded nanoassemblies with curcumin and assessed encapsulation efficiency, drug release, antitumoral activity, and intracellular trafficking.

Main Results:

• Developed ABPs nanoassemblies with dual-location acidic pH-responsive degradation.
• Achieved controlled degradation at tumoral pH and rapid degradation at endo/lysosomal pH.
• Demonstrated high encapsulation efficiency for curcumin and enhanced drug release at lower pH.
• Showcased promising antitumoral activity and effective intracellular delivery to cancer cells, with empty nanoassemblies showing no cytotoxicity.

Conclusions:

• The dual-location acidic pH-responsive degradation strategy offers a versatile platform for advanced tumor-targeted drug delivery.
• This approach enables individually controlled and synergistically enhanced therapeutic release profiles.
• The developed ABPs nanoassemblies hold significant potential for next-generation cancer therapy.