Extracellular vesicles involved in the crosstalk between apoptosis and ferroptosis revealed via a viscosity-sensitive fluorescent probe targeting lysosomes and nucleoli

Abstract

Advancements in cancer therapy have emerged through the combination of multiple signaling pathways, minimizing drug resistance and off-target effects. Therefore, diverse drug design strategies have been developed, including hybrid apoptosis/ferroptosis pathways. However, not much is known regarding their crosstalk, particularly regarding the details of intracellular and intercellular communication. Extracellular vesicles (EVs) play a crucial role in signal transduction and matter exchange among cells and are categorized into ectosomes, exosomes, and apoptotic bodies of varying sizes. The biogenesis and microenvironment of EVs are crucial for understanding their biological functions; however, they are still under debate. Herein, we used a fluorescent probe with viscosity sensitivity that targets lysosomes and nucleoli to detect viscosity alterations during apoptosis and ferroptosis, resulting in triggered green emission. Further fluorescent imaging of cells revealed crosstalk between apoptosis and ferroptosis, detecting apoptotic bodies originating from lysosomes and condensed nucleoli as EVs in hybrid apoptosis/ferroptosis pathways.