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Abstract
Cell death is closely related to various diseases, and monitoring and controlling cell death is a promising strategy to develop efficient therapy. Aggregation-induced emission luminogens (AIEgens) are ideal candidates for developing novel theranostic agents because of their intriguing properties in the aggregate state. The rational application of AIE materials in cell death-related research is still in its infancy but has shown great clinical potential. This review discussed the research frontier and our understanding of AIE materials in various subroutines of cell death, including apoptosis, necrosis, immunogenic cell death, pyroptosis, autophagy, lysosome-dependent cell death, and ferroptosis. We hope that the new insights can be offered to this growing field and attract more researchers to provide valuable contributions.
Highlights
regulated cell death (RCD) can be classified into various subroutines, namely, apoptosis, autophagydependent cell death (ADCD), necroptosis, pyroptosis, ferroptosis, immunogenic cell death (ICD), and lysosomedependent cell death (LDCD).[3]
This review highlighted the recent examples of Aggregationinduced emission luminogens (AIEgens) used in studying the mechanisms and functions of cell death and aimed to attract more attention in this critical frontier field
Many AIEgens were used as indicators and inducers for cell death subroutines, including apoptosis, necrosis, ICD, pyroptosis, autophagy, LDCD, and ferroptosis
Summary
Cell death (CD) is an irreversible degeneration of vital cellular functions culminating in loss of cellular integrity (Table 1).[1−3] According to traditional morphotype classification, cell death is classified into Types I, II, and III.[1,2] Type I cell death is called apoptosis, and it exhibits distinguishing morphological characteristics including cell shrinkage, chromatin condensation, nuclear fragmentation, membrane blebbing, and apoptotic bodies.[2,4] Type II cell death is named autophagydependent cell death (ADCD) and manifested by large-scale cytoplasmic vacuolization to culminate in lysosomal degradation and cell death.[1,5] Type III cell death corresponds to necrosis characterized by membrane integrity loss and subcellular organelle swelling.[2,6] Depending on control mechanisms, cell death can be divided into accidental cell death (ACD) and regulated cell death (RCD).[1−3] ACD is an instantaneous and biologically uncontrolled process corresponding to the plasma membrane breakdown caused by severe physical, chemical, or mechanical conditions.[2]. (LMP).[1,2] Importantly, LDCD introduced by LMP usually bypasses the classic caspase-dependent apoptosis pathway, providing a new promising anticancer strategy for overcoming apoptosis and drug resistant cancers.[3,103] Many lysosometargeted fluorescent AIEgens were used for tracking lysosomes,[104] photodynamic therapy,[105] and specific detection, such as subcellular organelle pH,[104] endogenous HClO,[106] heparin,[107] β-N-acetylhexosaminidase,[108] and carboxylesterases.[109] LMP can initiate or extend cell death processes, including apoptosis, ADCD, and ferroptosis.[2,105] For example, when the permeability of the lysosome decreases, the toxic iron stored in the lysosome is released into the cytoplasm, resulting in ferroptosis.[2] There were fewer research articles indicating LDCD probably because lysosome was related to many death processes,[110] and different cell death might occur in “mixed” variants.[2] It was possible that other death modes dominated, which led to the obscure of the LDCD process.[111]. The usage of AIE for ferroptosis is relatively rare, and there are many places worth discovering and exploring
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