APE1-Activated and NIR-II Photothermal-Enhanced Chemodynamic Therapy Guided by Amplified Fluorescence Imaging

The development of intelligent nanotheranostic technology that integrates diagnostic and therapeutic functions holds great promise for personalized nanomedicine. However, most of the nanotheranostic agents exhibit "always-on" properties and do not involve an amplification step, which may largely limit imaging contrast and restrict therapeutic efficacy. Herein, we construct a novel nanotheranostic platform (Hemin/DHPs/PDA@CuS nanocomposite) by assembling DNA hairpin probes (DHPs) and hemin on the surface of PDA@CuS nanosheets that enables amplified fluorescence imaging and activatable chemodynamic therapy (CDT) of tumors. The cancer-relevant APE1 triggers nucleic acid amplification with DHPs to generate activatable and amplified fluorescence signals for discriminating cancer cells from normal cells. Meanwhile, excessive G-quadruplex/hemin-based DNAzyme are also activated, and they function as Fenton-like catalysts to catalyze the production of highly toxic hydroxyl radicals (•OH) for CDT. Moreover, owing to the excellent photothermal conversion efficiency in the near-infrared-II (NIR-II) window, the PDA@CuS not only improves the catalytic performance of CDT but also furnishes PTT. A remarkable antitumor therapeutic effect is demonstrated both in vitro and in vivo. Therefore, the Hemin/DHPs/PDA@CuS nanocomposite is expected to provide a promising avenue for precise imaging-guided antitumor therapy.