A Versatile Method to Prepare Protein Nanoclusters for Drug Delivery

Nanocarriers based on natural biomaterials such as peptides and proteins have shown great advantages in the field of nanomedicine. However, the complicated preparation process and possible denaturation of proteins may limit their further applications. Herein, a novel method is developed to prepare protein nanocluster drug delivery system based on the self-aggregated property of proteins under the isoelectric point condition. The crosslinked protein nanoclusters, prepared by adding modified natural crosslinking agent polysaccharide, exhibit excellent stability and autofluorescent property in physiological conditions. Hemoglobin, a model protein, is chosen for preparation of drug-loaded nanoclusters. The as-prepared nanoclusters demonstrate a pH-responsive drug release behavior and can successfully deliver drugs into cancer cells. Moreover, this approach can be extended to various proteins, exemplifying the universal applicability of our new preparation method for protein-based nanoparticles.