Generalizable Strategy for Engineering Protein Particles with pH-Triggered Disassembly and Recoverable Protein...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Protein Engineering

Background:

• Protein particles are explored for therapeutic delivery due to their biocompatibility.
• Existing protein delivery systems often face challenges with protein functionality loss upon release.

Purpose of the Study:

• To develop a generalizable method for creating pH-cleavable protein particles.
• To ensure protein functionality is recovered after particle disassembly.
• To establish a new platform for therapeutic and drug delivery.

Main Methods:

• Utilized an acid-labile reversible cross-linker based on maleic anhydride chemistry.
• Assembled various proteins into pH-cleavable particles.
• Tested particle disassembly at pH < 6.5 and assessed protein functionality recovery, using glucose oxidase as a model.

Main Results:

• Achieved rapid disassembly of protein particles at mildly acidic pH.
• Demonstrated negligible cytotoxicity of the disassembled particles within cells.
• Reported over 97% recovery of enzymatic activity (glucose oxidase) after cross-linker cleavage.

Conclusions:

• A robust and facile strategy for engineering pH-cleavable protein particles was established.
• The developed protein particles offer a promising platform for therapeutic protein, small molecule drug, and nucleic acid delivery.
• The method ensures high recovery of protein functionality post-disassembly, minimizing therapeutic efficacy loss.