Biospecific Self‐Assembly of a Nanoparticle Coating for Targeted and Stimuli‐Responsive Drug Delivery

Biology provides a range of materials, mechanisms, and insights to meet the diverse requirements of nanomedicine. Here, a biologically based nanoparticle coating system that offers three characteristic features is reported. First, the coating can be self‐assembled through a noncovalent biospecific interaction mechanism between a lectin protein (Concanavalin A) and the polysaccharide glycogen. This biospecific self‐assembly enables the coating to be applied simply without the generation of covalent bonds. Second, glycoprotein‐based biofunctionality can be incorporated into the coating through the same noncovalent biospecific interaction mechanism. Here, the glycoprotein transferrin is incorporated into the coating since this moiety is commonly used to target cancer cells through a receptor‐mediated endocytosis mechanism. Third, the coating can be triggered to disassemble in response to a reduction in pH that is characteristic of endosomal uptake. In a proof‐of‐concept study, comparing coated and uncoated nanoparticles, model drug‐loaded nanoparticles (doxorubicin‐loaded mesoporous silica nanoparticles) are prepared and it is observed that the coated nanoparticle has enhanced cytotoxicity for cancer cell lines but attenuated cytotoxicity for noncancerous cell lines. These studies demonstrate that biology provides unique materials and mechanism appropriate to meet the needs for emerging applications in the medical and life sciences.