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.