Cytosolic Protein Delivery via Protein-Bound Microparticles Based on Anionic Boron Clusters and Cationic Polymers

Direct protein delivery to the cytosol facilitates immediate functional expression of proteins without the risks associated with gene introduction. However, the technology for delivering various proteins to the cytosol is still in its infancy. Herein, the formation of microparticles comprising anionic boron clusters and the cationic polymer hexadimethrine bromide (HDB) was demonstrated. In particular, the microparticles formed from dodecabromododecaborate clusters and HDB were confirmed to be bound with proteins. The protein-bound boron cluster/polymer-based microparticles (protein-bound BPMs) were internalized into cells via endocytosis. Upon internalization, the protein-bound BPMs released the proteins with different isoelectric points and sizes into the cytosol. Furthermore, an enzyme was delivered by protein-bound BPMs into the cytosol of various cell types while maintaining its functional activity. This method shows considerable promise for delivering diverse proteins to a variety of cell types, potentially advancing the field of protein-based therapeutics. Our findings open new avenues for utilizing boron clusters in cytosolic delivery systems.