A dual-functional photosensitizer for mitochondria-targeting photodynamic therapy and synchronous polarity monitoring

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Detail(s)

Original languageEnglish
Pages (from-to)11259-11264
Journal / PublicationJournal of Materials Chemistry B
Volume12
Issue number43
Online published26 Sept 2024
Publication statusPublished - 21 Nov 2024

Abstract

Mitochondria-targeting photodynamic therapy (PDT) has been validated as an effective strategy for inducing cell death through the disruption of mitochondrial function. The mitochondrial microenvironment, such as viscosity, polarity, pH and proteins, undergoes dynamic changes during PDT treatment, and investigating these parameters is crucial for comprehending the intrinsic mechanisms at the cellular level. In this context, disclosure of mitochondrial microenvironment alterations holds significant importance. Nevertheless, a probe capable of visualizing mitochondrial polarity fluctuations during PDT treatment has not been reported. Importantly, a dual-functional photosensitizer (PS) with polarity detection capability is highly advantageous as it can mitigate potential metabolic and localization disparities between the PS and the polarity probe, thus improving the accuracy of detection. In this contribution, a series of potential PSs were prepared by integrating the 2,1,3-benzoxadiazole (BD) scaffold with various heteroatom-incorporated electron-withdrawing groups. Among them, BDI exhibited potent phototoxicity against cancer cells and remarkable sensitivity to polarity changes, establishing it as a dual-functional PS for both photodynamic therapy and polarity detection. Leveraging its polarity detection capability, BDI successfully discriminated mitochondrial polarity discrepancy between cancer cells and normal cells, and indicated mitochondrial polarity fluctuations during drug-induced mitophagy. Crucially, BDI was employed to unveil mitochondrial polarity variations during PDT treatment, underscoring its dual function. Altogether, the meticulous design of the dual-functional PS BDI offers valuable insights into intracellular microenvironment variations during the PDT process, thereby enhancing our understanding and guiding the optimization of PDT treatment.
© The Royal Society of Chemistry 2024

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