A Smart Photosensitizer–Cerium Oxide Nanoprobe for Highly Selective and Efficient Photodynamic Therapy

Abstract

Cerium oxide (CeO _x) with a reversible surface Ce³⁺/Ce⁴⁺ redox pair has played an important role in catalytic reactions, whereas catalase mimetics of CeO _x have attracted little attention in the field of biotherapy. Herein, a smart photosensitizer-cerium oxide nanoprobe was developed to represent a promising paradigm in high-performance photodynamic therapy. The photosensitizer was linked to CeO _x nanoparticles through a substrate peptide (EGPLGVRGK) of matrix metalloproteinase-2 (MMP-2). The smart nanoprobe could be converted from the "silent state" before arriving at the cancer cells to the "activated state" within the cells to turn on the fluorescence and ¹O₂ generation when the peptide linker (EGPLGVRGK) was cut by the cancer biomarker MMP-2. Moreover, CeO _x played the role of an excellent catalase-like compound to decompose endogenous hydrogen peroxide to relieve tumor hypoxia. Via the conventional application of CeO _x, our study showed innovatively how a smart nanoprobe could relieve tumor hypoxia and achieve a therapeutic effect for highly selective and efficient personalized treatment.