Light-Controlled Intracellular Synthesis of Poly(luciferin) Polymers Induces Cell Paraptosis

Accumulation of misfolded proteins challenges cellular proteostasis and is implicated in aging and chronic disorders. Cancer cells, moreover, face an elevated level of basal proteotoxic stress; hence, exacerbating endoplasmic reticulum (ER) stress has been shown to induce programmed cell death while enhancing anticancer immunogenicity. We hypothesize that hydrophobic abiotic macromolecules can trigger a similar stress response. Most polymers and nanoparticles, however, are sequestered in endo/lysosomes after endocytosis, which prevents their interaction with the proteostasis machinery. We adopted an