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Published on: September 17, 2013
Three in One: Viscosity-Sensitive Ruthenium(II) Complexes for Photodynamic Anticancer by Activating Pyroptosis with
Xiurong Ma1, Guixi Wang2, Qian Zhou1
1School of Chemical Science and Technology, Key Laboratory of Medicinal Chemistry for Natural Resource of Yunnan, University Ministry of Education, Yunnan University, Kunming, Yunnan 650091, China.
Abstract:
The development of a photosensitizer (PS) integrating real-time therapeutic monitoring capability represents a critical advancement in precision photodynamic therapy (PDT). Herein, three ruthenium(II)-triphenylamine photosensitizers (Ru1-3) were designed and synthesized. Detailed antitumor mechanism investigations revealed that Ru1 and Ru3 activated caspase-1, induced gasdermin D (GSDMD) cleavage and mitochondrial membrane potential (MMP) depolarization, and triggered cell pyroptosis. An increase in the luminescence intensity of Ru1 and Ru3 was observed during cell pyroptosis, indicating a significant augmentation of cytoplasmic viscosity during pyroptosis. Moreover, two-photon excitation experiments verified that they possessed photocytotoxicity in 3D multicellular tumor spheroids (MCTSs), and a similar luminescence amplification correlated with pyroptosis progression was observed. In vivo studies confirmed that Ru3 exhibits superior PDT efficacy and provides real-time feedback on treatment response via its self-reporting luminescence characteristics. This work provides new insights into the design and implementation of multifunctional photosensitizers for tumor cell pyroptosis with real-time therapeutic monitoring and two-photon imaging.
