Enhanced Sonodynamic Therapy for Deep Tumors Using a Self-Assembled Organoplatinum(II) Sonosensitizer

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 (1O2) generation due to a significantly
enhanced singlet–triplet intersystem crossing (ISC). This generation
of 1O2 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.