Nano-assembly of bovine serum albumin driven by rare-earth-ion (Gd) biomineralization for highly efficient photodynamic therapy and tumor imaging

Biomineralization of a rare earth ion (Gd) is first employed to assemble bovine serum albumin (BSA) into sub-50 nm nanoparticles (Gd@ BSA) for theranostic applications, via a straightforward and reproducible strategy. Combination of Gd ions with BSA under mild conditions results in the formation of the Gd@ BSA nanosystem, which has been used as the scaffold material to encapsulate a photosensitiser (Ce6) with high efficiency up to 20 wt%. Beyond playing an important role in the assembled process, the incorporation of Gd affords the potential MRI and fluorescence imaging capability of Gd@ BSA-Ce6 nanoparticles. In vivo MRI allowed real-time imaging in tumor-bearing mice and showed advantages in terms of circulation time, compared with commercially used Gd-DTPA. Gd@ BSA-Ce6 nanoparticles exhibited enhanced tumor-specific distribution, through enhanced permeability and retention effect, and complete cure of tumor-bearing mice after intravenous injection. The nanoparticles did not produce systemic toxicity as revealed by biodistribution and histology toxicity analyses. The results demonstrate the great potential of Gd@ BSA-Ce6 nanoparticles as theranostic agents due to their excellent imaging and tumor-growth-inhibition properties.