Mitochondrial DNA-targeted triphenylamine-thiophene (TPATP)-derived ligands boost type-I/II photodynamic therapy for triple-negative breast cancer.

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Tác giả: Ming-Hao Hu, Zhi-Ling Liang, Yong-Si Liu, Xiao-Dong Wang

Ngôn ngữ: eng

Ký hiệu phân loại: 232.964 Burial

Thông tin xuất bản: France : European journal of medicinal chemistry , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 685414

Triple-negative breast cancer (TNBC) is aggressive with poor prognosis. Current strategies include chemotherapy, surgery, and radiotherapy, but face challenges like suboptimal outcomes, low survival, and drug resistance. Thus, novel TNBC therapies are crucial. Activity-based photodynamic therapy (PDT) is a highly regarded cancer treatment strategy known for its spatiotemporal precision, making it a promising option for the treatment of TNBC. In this study, we designed and synthesized three triphenylamine-thiophene (TPATP)-derived ligands binding to mitochondrial DNA G4 (mtG4), which were able to label mitochondria in TNBC cells under red-light excitation, and demonstrated significant phototoxicity through type-I/II process under white-light irradiation, hinting at dual-functional potential for PDT and imaging. The optimal ligand, TP2, was demonstrated to disrupt mitochondrial functions under white-light irradiation, leading to MMP loss, ATP reduction, ROS increase, which further triggered significant apoptosis in TNBC cells.
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