Single-protein-based theranostic nanosystem within sub-10 nm scale for tumor imaging and therapy

Abstract

A single-protein-based theranostic nanosystem (SPTN) based on non-covalent interaction between bovine serum albumin (BSA), gadolinium (Gd) and the anticancer hydrophobic drug doxorubicin (DOX) was designed and developed via a facile, environmentally benign approach. Gd was incorporated into the structure of BSA via a simple biomineralization process, while DOX was encapsulated in Gd–BSA nanoparticles via hydrophobic interaction between DOX and BSA, as well as a coordination effect between DOX and Gd. The whole SPTN system was kept in one single BSA molecule to form a single protein based nanosystem with an overall size of around 7 nm favorable for potential renal clearance. The SPTN nanosystem showed not only robust biocompatibility, excellent T₁-weighted MR imaging effect but also fine pH-responsive drug release characteristics. Furthermore, in vivo therapeutic efficacy experiment showed that the nanoparticle DOX–Gd–BSA had an obvious therapeutic efficacy toward hepatoma tumor bearing mice.