Sinian Zheng,1 Cong Li,2 Jiayu Chen,3 Kuo Zhang,1 Xiaobo Cui,1 Rubing Li,1 Zeming Weng1 1Department of Urology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, Peopleâs Republic of China; 2Department of Urology, Yuyao Hospital of Traditional Chinese Medicine, Ningbo, Zhejiang, Peopleâs Republic of China; 3Operating Room, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, Peopleâs Republic of ChinaCorrespondence: Rubing Li, Email nblirb@126.com Zeming Weng, Email ZemingWeng1@126.comIntroduction: 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@TiO2 heterojunctions and characterized their morphology, electronic structure, and ROS generation capacity. In vitro, OSRC-2 cells were treated with HKUST-1@TiO2 ± ultrasound; cell viability, proliferation, apoptosis, and intracellular ROS were assessed. In vivo, nude mice bearing OSRC-2 xenografts received HKUST-1@TiO2 ± ultrasound; tumor growth, histopathology, and biosafety markers were analyzed.Results: HKUST-1@TiO2 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@TiO2 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.Keywords: renal cell carcinoma, sonodynamic therapy, metal-organic frameworks, heterojunction, reactive oxygen species, titanium dioxide
Zheng et al. (Wed,) studied this question.