Release Date:5/22/2023 8:09:00 PM

Hypoxia, the hallmark of malignant tumors, has been recognized as a major obstacle for photodynamic therapy (PDT). Precisely targeting cancer cells in intricate biological scenarios by a hypoxia-resistant photosensitizer (PS) is the cornerstone to conquer the inevitable tumor recurrence and metastasis. Herein, we describe an organic NIR-II PS (TPEQM-DMA) possessing potent type-I phototherapeutic efficacy to overcome the intrinsic pitfalls of PDT in combating hypoxic tumors. TPEQM-DMA exhibited prominent NIR-II emission (>1000 nm) with an aggregation-induced emission feature and efficiently produced superoxide anion and hydroxyl radical in the aggregate state under white light irradiation exclusively through a low-O2-dependent type-I photochemical process. The suitable cationic nature assisted TPEQM-DMA to accumulate in cancerous mitochondria. Meanwhile, the PDT of TPEQM-DMA impaired the cellular redox homeostasis, led to the mitochondrial dysfunction, and raised the level of lethal peroxidized lipids, which induced cellular apoptosis and ferroptosis. This synergistic cell death modality enabled TPEQM-DMA to suppress the growth of cancer cells, multicellular tumor spheroids, and tumors. To improve the pharmacological properties of TPEQM-DMA, TPEQM-DMA nanoparticles were prepared by encapsulation of polymer. In vivo experiments proved the appealing NIR-II fluorescence imaging-guided PDT effect of TPEQM-DMA nanoparticles for tumors.



Congratulations to Professor Benzhong Tang, Na Zhao, and co-authors from The Chinese University of Hong Kong and Shaanxi Normal University, China for their excellent work published in ACS Nano (IF=18.03)!



InvivoChem is proud to provide Professor Benzhong Tang’s team with our high-quality product Belnacasan (VX765) (Cat #: V0024; CAS #: 273404-37-8, prodrug of VRT-043198 and caspase-1 inhibitor) for this research.



References: ACS Nano. 2023 May 23;17(10):9110-9125. doi: 10.1021/acsnano.2c12319.

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