Enhanced Sonodynamic Therapy for Deep Tumors Using a Self-Assembled Organoplatinum(II) Sonosensitizer
Haobing Wang, Dan Li, Hanqiang Wang, Qingyan Ren, Yue Pan, Anyi Dao, Deliang Wang, Zhigang Wang, Pingyu Zhang, Huaiyi Huang
Abstract
Despite the promising advances in photodynamic therapy (PDT), it remains challenging to target and treat deep-seated solid tumors effectively. Herein, we developed an organoplatinum(II) complex ( Pt-TPE ) with self-assembly properties for sonodynamic therapy (SDT). Pt-TPE forms a nanofiber network structure through Pt–Pt and π–π stacking interactions. Notably, under ultrasound (US), Pt-TPE demonstrates unique self-assembly-induced singlet oxygen ( 1 O 2 ) generation due to a significantly enhanced singlet–triplet intersystem crossing (ISC). This generation of 1 O 2 occurs exclusively in the self-assembled state of Pt-TPE . Additionally, Pt-TPE exhibits sono-cytotoxicity against cancer cells by impairing mitochondrial membrane potential (MMP), inhibiting glucose uptake, and aerobic glycolysis. Furthermore, US-activated Pt-TPE significantly inhibits deep solid tumors in mice, achieving remarkable therapeutic efficacy even at penetration depths greater than 10 cm. This study highlights the potential of self-assembled metal complexes to enhance the efficacy of SDT for treating deep tumors.