Haobing Wang, Dan Li, Hanqiang Wang, Qingyan Ren, Yue Pan, Anyi Dao, Deliang Wang, Zhigang Wang, Pingyu Zhang, Huaiyi Huang
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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.
期刊介绍:
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.