Transferrin Protein Corona-Modified CuGd Core–Shell Nanoplatform for Tumor-Targeting Photothermal and Chemodynamic Synergistic Therapies

Herein, we developed a novel transferrin protein corona (Tpc)-modified CuGd nanoplatform (Tpc-CuGd) for tumor-targeting photothermal (PT) and chemodynamic synergistic therapy. In addition, Tpc-CuGd had an ultrahigh PT conversion efficiency (∼55.6%) and excellent PT stability. By the calculation, the Fenton-catalytic activity of Tpc-CuGd was approximately 13.6 times that of classical ultrasmall iron oxide, endowing strong chemodynamic therapy ability in the tumor. Upon internalization of Tpc-CuGd nanoparticles (NPs), an abundance of Cu(II) was released from Tpc-CuGd and then was quickly reduced to high Fenton-catalytic activity of Cu(I) by elemental copper and cellular GSH. Next, the generated Cu(I) quickly catalyzed H2O2 into highly toxic •OH, causing mitochondria damage and inducing cancer cell death. In addition, the systemic delivery of Tpc-CuGd significantly inhibited tumor growth and showed a very low toxicity. Notably, the PT effect of Tpc-CuGd NPs not only promoted their tumor inhibitory capability but also significantly restricted the continued growth of the tumor after the discontinuation of the treatment. In addition, Tpc-CuGd significantly strengthened the T1-weighted signal of tumors and realized accurate cancer diagnosis. Therefore, this nanoplatform could be a great promising candidate for PT and chemodynamic synergistic theranostics.