Interaction between CD44 and highly condensed hyaluronic acid through crosslinking with proteins

Proteins and nucleic acids derived from bioresources have become a novel medical modality. However, the intrinsic features of proteins, such as their high molecular weight and polarity, impede their passage through the cell membrane. In this study, to deliver proteins to cancer cells, we prepared conjugates consisting of bovine serum albumin (BSA) and hyaluronic acid (HA). These conjugates contained multiple BSA and HA molecules and adopted a highly condensed structure by crosslinking through BSA. When the interaction between the HA-BSA conjugates and recombinant CD44 (rCD44) was examined using a quartz crystal microbalance, the conjugates induced a larger decrease of frequency change than HA. CT26 cells treated with FITC-labeled HA-BSA conjugates showed high fluorescence intensity. The uptake of the conjugates decreased upon adding excess HA. Therefore, the conjugates and nanoparticles with densely packed HA structures could be a potent and effective platform for delivering proteins to cancer tissues.