Design Principles of Microparticles Based on Superchaotropic Boron Clusters and Quaternary Ammonium-Based Cationic Polymers for Cytosolic Protein Delivery

Superchaotropicity provides a carrier for cytosolic protein delivery that overcomes the limitation on the deliverable range imposed by electrostatic or hydrophobic complementarity in existing carriers. However, the types of molecules that can adapt to the carrier and the mechanism by which the carrier is formed have not yet been clarified. Here, we show that the superchaotropic anionic boron cluster B12Br122− assembles with diverse quaternary ammonium-based cationic polymersregardless of degree of polymerization, structure, or topologyinto protein-loaded boron cluster/polymer-based microparticles (BPMs) that are internalized by cells and release protein into the cytosol. The delivery profile, tunable through polymer identity, degree of polymerization, and concentration, accommodates proteins differing in molecular weight and isoelectric point. In contrast, tertiary ammonium polymers, whose protonated N−H groups act as competing hydrogen-bond donors, form BPMs poorly. These results establish the quaternary ammonium group as an important design element for protein delivery by superchaotropic boron clusters.