Intracellular Photoactivation of Caspase-3 by Molecular Glues for Spatiotemporal Apoptosis Induction

• DOI: 10.1021/jacs.0c01823
• Publication Date: 2020-04-10T17:51:04Z
• Authors: Nina B. Hentzen; Rina Mogaki; Saya Otake; Kou Okuro; Takuzo Aida
• Keywords: CASP; Nanopore

Caspase-3 (Casp-3) is an enzyme that efficiently induces apoptosis, a form of programmed cell death. We report dendritic molecular glue PCGlue enables intracellular delivery Casp-3 and its photoactivation. carrying multiple guanidinium (Gu+) ion pendants via photocleavable linkages can tightly adhere to deliver it into the cytoplasm mainly by direct penetration through plasma membrane. Casp-3, whose surface covered PCGlue, unable interact with cellular substrates therefore not induce apoptosis. However, upon exposure UV or two-photon near-infrared (NIR) light, cleaved off liberate triggering apoptotic signaling cascade. This photoactivation allows spatiotemporal induction apoptosis in irradiated cells.