Design of self-assembled glycopolymeric zwitterionic micelles as removable protein stabilizing agents

• Published in: Nanoscale advances 2023-03, Vol.5 (6), p.1767-1775
• Main Authors: Rajan, Robin, Matsumura, Kazuaki
• Format: Article
• Language: English
• Subjects: Chemistry
• ISSN: 2516-0230; 2516-0230
• DOI: 10.1039/d3na00002h

Developing stabilizers that protect proteins from denaturation under stress, and are easy to remove from solutions, is a challenge in protein therapeutics. In this study, micelles made of trehalose, a zwitterionic polymer (poly-sulfobetaine; poly-SPB), and polycaprolactone (PCL) were synthesized by a one-pot reversible addition-fragmentation chain-transfer (RAFT) polymerization reaction. The micelles protect lactate dehydrogenase (LDH) and human insulin from denaturation due to stresses like thermal incubation and freezing, and help them retain higher-order structures. Importantly, the protected proteins are readily isolated from the micelles by ultracentrifugation, with over 90% recovery, and almost all enzymatic activity is retained. This suggests the great potential of poly-SPB-based micelles for use in applications requiring protection and removal as required. The micelles may also be used to effectively stabilize protein-based vaccines and drugs. Polysulfobetaine, trehalose, and polycaprolactone were combined to create micelles that stabilize proteins and can be easily removed by ultracentrifugation. The three components work synergistically to enhance protein protection within the micelles.