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      Type I photosensitizers based on phosphindole oxide for photodynamic therapy: apoptosis and autophagy induced by endoplasmic reticulum stress†

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      Chemical Science
      The Royal Society of Chemistry

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          Abstract

          Photodynamic therapy (PDT) is considered a pioneering and effective modality for cancer treatment, but it is still facing challenges of hypoxic tumors. Recently, Type I PDT, as an effective strategy to address this issue, has drawn considerable attention. Few reports are available on the capability for Type I reactive oxygen species (ROS) generation of purely organic photosensitizers (PSs). Herein, we report two new Type I PSs, α-TPA-PIO and β-TPA-PIO, from phosphindole oxide-based isomers with efficient Type I ROS generation abilities. A detailed study on photophysical and photochemical mechanisms is conducted to shed light on the molecular design of PSs based on the Type I mechanism. The in vitro results demonstrate that these two PSs can selectively accumulate in a neutral lipid region, particularly in the endoplasmic reticulum (ER), of cells and efficiently induce ER-stress mediated apoptosis and autophagy in PDT. In vivo models indicate that β-TPA-PIO successfully achieves remarkable tumor ablation. The ROS-based ER stress triggered by β-TPA-PIO-mediated PDT has high potential as a precursor of the immunostimulatory effect for immunotherapy. This work presents a comprehensive protocol for Type I-based purely organic PSs and highlights the significance of considering the working mechanism in the design of PSs for the optimization of cancer treatment protocols.

          Abstract

          Phosphindole oxide-based photosensitizers with Type I reactive oxygen species generation ability are developed and used for endoplasmic reticulum stress-mediated photodynamic therapy of tumors.

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          Author and article information

          Journal
          Chem Sci
          Chem Sci
          SC
          CSHCBM
          Chemical Science
          The Royal Society of Chemistry
          2041-6520
          2041-6539
          2 March 2020
          7 April 2020
          2 March 2020
          : 11
          : 13
          : 3405-3417
          Affiliations
          [a] State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, South China University of Technology Guangzhou 510640 China mszjzhao@ 123456scut.edu.cn
          [b] Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430074 China
          [c] Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences Wuhan 430074 China
          [d] Department of Chemistry, The Hong Kong University of Science & Technology Kowloon Hong Kong China
          Author information
          https://orcid.org/0000-0002-2837-1976
          https://orcid.org/0000-0002-6556-2034
          https://orcid.org/0000-0002-0618-6024
          https://orcid.org/0000-0002-0293-964X
          Article
          d0sc00785d
          10.1039/d0sc00785d
          8515424
          34745515
          f21b4cd1-6c69-425a-b177-728c46c62620
          This journal is © The Royal Society of Chemistry
          History
          : 10 February 2020
          : 20 February 2020
          Page count
          Pages: 13
          Funding
          Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
          Award ID: 21788102
          Funded by: Natural Science Foundation of Guangdong Province, doi 10.13039/501100003453;
          Award ID: 2019B030301003
          Categories
          Chemistry
          Custom metadata
          Paginated Article

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