Cerium-Crosslinked Carbon Dot Nanozymes with Catalase-like Activity for Imaging-Guided ROS Regulation and Therapy of Testicular Teratoma
Male infertility is increasingly recognized as a global health concern, with oxidative stress identified as one of its major pathological drivers. Excessive reactive oxygen species (ROS) can impair spermatogenesis, damage testicular tissue, and contribute to the onset and progression of testicular disorders, including germ-cell tumors. Among these, testicular teratoma represents a significant clinical challenge due to its complex cellular composition, high ROS dependence, and limited responsiveness to conventional therapeutic strategies. Developing multifunctional nanoplatforms capable of both regulating ROS levels in the testis and inducing tumor-specific ROS-based cytotoxicity offers an attractive approach for simultaneous protection and treatment. In this work, catalase-mimetic cerium–crosslinked carbon dot nanozymes were engineered as an integrated system for imaging-guided ROS modulation and therapeutic intervention in testicular teratoma. Yellow carbon dots (yCDs) were synthesized from o-phenylenediamine and taurine via a one-pot hydrothermal reaction, followed by self-assembly with Ce³⁺ to produce yCD/Ce nanozymes. Cerium incorporation endowed the nanozymes with multiple complementary enzyme-like functions—including superoxide dismutase-like, catalase-like, and peroxidase-like activities—enabling tailored conversion of intracellular •O₂⁻ and H₂O₂ into either detoxified products or highly reactive •OH radicals under tumor-specific conditions. The nanozymes exhibited intrinsic fluorescence for cellular imaging, strong antioxidants and anti-inflammatory effects beneficial for testicular microenvironment protection, and glutathione depletion that amplified chemodynamic therapeutic efficacy. Cellular studies revealed efficient internalization of yCD/Ce nanozymes by cancer cells and dynamic redox cycling between Ce³⁺/Ce⁴⁺, facilitating potent ROS regulation and tumor-selective ROS amplification. Collectively, this multifunctional platform integrates diagnostic imaging, ROS scavenging to protect healthy testicular tissue, and ROS-mediated cytotoxicity for targeted elimination of testicular teratoma, offering a promising strategy for addressing male reproductive disorders associated with oxidative stress and testicular malignancy. Keywords: carbon dots; nanozymes; tumor-microenvironment, ROS regulation; Testis; GSH depletion