title: Light-Induced Translocation of a Conjugated Polyelectrolyte in Cells: From Fluorescent Probe to Anticancer Agent.
abstract: Dual-functional probes, which not only enable visualization of diseased cells but also induce therapeutic cellular responses, are essential to biological studies. In the current work, a conjugated polyelectrolyte, PPET3-N2, was designed and synthesized as a dual-functional probe. The poly(phenylene ethynylene) terthiophene polymer backbone contributes to the polymer's light-harvesting property to ensure the strong fluorescence as well as photosensitization, whereas quantanary ammonium side chains interact with target organelle for localization. As a fluorescent probe, PPET3-N2 was endocytosed to lysosomes through clathrin-mediated endocytosis (CME) and macropinocytosis (MPC) pathways. Colocalization of the probe with commercial fluorescent lysosome labels confirmed that this probe localized on lysosomes with high specificity and photostability. Real-time monitoring of autolysosome formation in autophagic cells was also demonstrated, providing a viable platform for cell-based screening of autophagy inhibitors. Finally, as a photosensitizer, PPET3-N2 can efficiently generate singlet oxygen in living cells upon irradiation of white light, leading to the destruction of lysosome membrane and release of ROS and lysosomal enzymes in cytoplasma, causing cell death.
authors.affiliation: Department of Chemistry and ‡School of Pharmaceutical Sciences, Tsinghua University , Beijing 100084, P. R. China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, ∥Open FIESTA Center, and ⊥The Key Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen 518055, P. R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Chemistry and ‡School of Pharmaceutical Sciences, Tsinghua University , Beijing 100084, P. R. China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, ∥Open FIESTA Center, and ⊥The Key Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen 518055, P. R. China.
authors.forename: Naihan
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Chemistry and ‡School of Pharmaceutical Sciences, Tsinghua University , Beijing 100084, P. R. China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, ∥Open FIESTA Center, and ⊥The Key Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen 518055, P. R. China.
authors.forename: Chunyan
authors.identifier: http://orcid.org/0000-0002-4263-2175
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Chemistry and ‡School of Pharmaceutical Sciences, Tsinghua University , Beijing 100084, P. R. China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, ∥Open FIESTA Center, and ⊥The Key Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen 518055, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Chemistry and ‡School of Pharmaceutical Sciences, Tsinghua University , Beijing 100084, P. R. China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, ∥Open FIESTA Center, and ⊥The Key Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen 518055, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Chemistry and ‡School of Pharmaceutical Sciences, Tsinghua University , Beijing 100084, P. R. China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, ∥Open FIESTA Center, and ⊥The Key Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen 518055, P. R. China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemistry and ‡School of Pharmaceutical Sciences, Tsinghua University , Beijing 100084, P. R. China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, ∥Open FIESTA Center, and ⊥The Key Lab in Health Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen 518055, P. R. China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents; D001343:Autophagy; D005456:Fluorescent Dyes; D008247:Lysosomes; D000071228:Polyelectrolytes / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D000071228:Polyelectrolytes
keywords: autolysosome; autophagy; conjugated polyelectrolyte; singlet oxygen; translocation