Abstract
INTRODUCTION: Renal cell carcinoma (RCC) is a common urinary malignancy with high postoperative recurrence, and current therapies are limited by toxicity or insufficient efficacy. Efficient sonodynamic therapy (SDT) strategies capable of generating reactive oxygen species (ROS) are urgently needed. This study aimed to develop a high-performance MOF-based heterojunction sonosensitizer to enhance ROS generation and achieve effective anti-tumor activity. METHODS: We synthesized HKUST-1@TiO(2) heterojunctions and characterized their morphology, electronic structure, and ROS generation capacity. In vitro, OSRC-2 cells were treated with HKUST-1@TiO(2) ± ultrasound; cell viability, proliferation, apoptosis, and intracellular ROS were assessed. In vivo, nude mice bearing OSRC-2 xenografts received HKUST-1@TiO(2) ± ultrasound; tumor growth, histopathology, and biosafety markers were analyzed. RESULTS: HKUST-1@TiO(2) exhibited efficient heterojunction formation, which enhanced charge separation and ROS production under ultrasound. In vitro, the combination treatment significantly reduced cell viability, decreased Ki67-positive area, and increased the number of TUNEL-positive cells. Intracellular ROS staining confirmed effective ROS accumulation in tumor cells. In vivo, tumor volume and weight were significantly reduced, with no detectable organ toxicity. CONCLUSION: HKUST-1@TiO(2) heterojunctions effectively augment SDT through enhanced intracellular ROS generation, inducing tumor cell apoptosis and inhibiting proliferation. This study addresses the unmet need for efficient and safe SDT for RCC and provides a promising strategy with translational potential.