Real-time imaging mitochondrial viscosity dynamic during mitophagy mediated by photodynamic therapy

Abstract

Photodynamic therapy has been generally developed and approved as a promising theranostic technique in recent years, which requires photosensitizers to bear high efficiency of reactive oxygen species production, precisely targeting ability and excellent biocompatibility. The real-time monitoring the microenvironments such as viscosity dynamic involved in mitophagy mediated by photodynamic therapy is significantly important to understand therapeutic process but barely reported. In this work, a pyridinium-functionalized triphenylamine derivative, (E)-4-(2-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)vinyl)-1-methylpyridin-1-ium iodide (Mito-I), was exploited as photosensitizer for mitochondria-targeted photodynamic therapy and as fluorescent probe for imaging the mitochondrial viscosity dynamic during mitophagy simultaneously. The results indicated that the additional phenyl ring in Mito-I was beneficial to promote its efficiency of singlet oxygen production. The excellent capability of targeting mitochondria and singlet oxygen generation allowed Mito-I for the specifically mitochondria-targeted photodynamic therapy. Moreover, Mito-I displayed off-on fluorescence response to viscosity with high selectivity and sensitivity. The observed enhancement in fluorescence intensity of Mito-I revealed the increasingly mitochondrial viscosity during mitophagy mediated by the photodynamic therapy of Mito-I. As a result, this work presents a rare example to realize the mitochondria-targeting photodynamic therapy as well as the real-time monitoring viscosity dynamic during mitophagy, which is of great importance for the basic medical research involved in photodynamic therapy.

Keywords: Mitochondrial targeting; Mitophagy; Photodynamic therapy; Pyridinium-based triphenylamine; Singlet oxygen; Viscosity probe.