Polysiloxane probes with main chain modifications regulating subcellular organelles localization for dynamic observation of lysosomal and mitochondrial interactions during cellular hypoxia

Abstract

As an important pathological state, hypoxia is closely associated with the occurrence of numerous diseases. The degree of hypoxia can reflect the related pathological conditions. The expression of heme oxygenase-1 (HO-1) will lead to the increase of endogenous carbon monoxide (CO) during hypoxia. Abnormal concentrations of CO involved in regulating various physiological activities of cells may result in the damage of organelles from lysosomes to mitochondria and further disrupt the normal communication between organelles. However, normal intercellular communication and interactions have profound significance for the dynamic equilibrium of the intracellular environment. Hence, it is a challenging task to develop new tools to visualize the effect of CO on the interaction of different organelles during hypoxia. In this paper, we designed fluorescent probes that could switch between lysosomes and mitochondria by using polysiloxane platforms (P1-CORM-Lyso and P1-CORM-Mito) for the first time. P1-CORM-Lyso and P1-CORM-Mito successfully enabled monitor the CO generated during anoxia with excellent biocompatibility. We expect that this switchable targeting silicon-based fluorescent materials will open up new fields for the design of new fluorescent probes and get a deeper understanding of the cellular hypoxia process.