Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor-Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity
Xie Huang
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorMingquan Gao
School of Medicine, University of Electronic Science and Technology of China, Department of Radiation Oncology, Sichuan Key Laboratory of Radiation Oncology Sichuan Cancer Hospital, Chengdu, 610041 China
Search for more papers by this authorHaiyan Xing
Department of Pharmacy, Daping Hospital, Third Military Medical University (Army Medical University), Daping, Chongqing, 400042 China
Search for more papers by this authorZaizhi Du
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorZifei Wu
School of Medicine, University of Electronic Science and Technology of China, Department of Radiation Oncology, Sichuan Key Laboratory of Radiation Oncology Sichuan Cancer Hospital, Chengdu, 610041 China
Search for more papers by this authorJing Liu
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorTao Li
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorJiang Cao
School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorXiaochao Yang
School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorRong Li
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorCorresponding Author
Weidong Wang
School of Medicine, University of Electronic Science and Technology of China, Department of Radiation Oncology, Sichuan Key Laboratory of Radiation Oncology Sichuan Cancer Hospital, Chengdu, 610041 China
E-mail: [email protected], [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Junping Wang
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
E-mail: [email protected], [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Shenglin Luo
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
E-mail: [email protected], [email protected], [email protected]
Search for more papers by this authorXie Huang
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorMingquan Gao
School of Medicine, University of Electronic Science and Technology of China, Department of Radiation Oncology, Sichuan Key Laboratory of Radiation Oncology Sichuan Cancer Hospital, Chengdu, 610041 China
Search for more papers by this authorHaiyan Xing
Department of Pharmacy, Daping Hospital, Third Military Medical University (Army Medical University), Daping, Chongqing, 400042 China
Search for more papers by this authorZaizhi Du
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorZifei Wu
School of Medicine, University of Electronic Science and Technology of China, Department of Radiation Oncology, Sichuan Key Laboratory of Radiation Oncology Sichuan Cancer Hospital, Chengdu, 610041 China
Search for more papers by this authorJing Liu
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorTao Li
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorJiang Cao
School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorXiaochao Yang
School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorRong Li
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
Search for more papers by this authorCorresponding Author
Weidong Wang
School of Medicine, University of Electronic Science and Technology of China, Department of Radiation Oncology, Sichuan Key Laboratory of Radiation Oncology Sichuan Cancer Hospital, Chengdu, 610041 China
E-mail: [email protected], [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Junping Wang
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
E-mail: [email protected], [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Shenglin Luo
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038 China
E-mail: [email protected], [email protected], [email protected]
Search for more papers by this authorAbstract
Cancer phototherapy activates immunogenic cell death (ICD) and elicits a systemic antitumor immune response, which is an emerging approach for tumor treatment. Most available photosensitizers require a combination of immune adjuvants or checkpoint inhibitors to trigger antitumor immunity because of the immunosuppressive tumor microenvironment and the limited phototherapeutic effect. A class of tumor-targeting heptamethine cyanine photosensitizers modified with an endoplasmic reticulum (ER)-targeting group (benzenesulfonamide) are synthesized. Phototherapy of tumor cells markedly amplifies ER stress and promotes tumor antigen release, as the ER is required for protein synthesis, secretion, and transport. More importantly, different electron-donating or -withdrawing substitutions are introduced into benzenesulfonamide to modulate the nonradiative decay pathways through intramolecular charge transfer, including singlet–triplet intersystem crossing (photodynamic effect) and internal thermal conversion (photothermal effect). Thus, a heptamethine cyanine photosensitizer containing a binitro-substituted benzenesulfonamide (ER-Cy-poNO2) is identified that preferentially accumulates in the ER of tumor cells. It significantly enhances the phototherapeutic effect by inducing excessive ER stress and robust ICD. Consequently, this small molecular photosensitizer triggers a sufficient antitumor immune response and effectively suppresses the growth of both primary and distant metastatic tumors, whereas no apparent toxicity is observed. This heptamethine cyanine photosensitizer has the potential to enhance cancer-targeted immunotherapy.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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| smll202202728-sup-0001-SuppMat.pdf7.5 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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