Self-Immolative Photosensitizers for Self-Reported Cancer Phototheranostics
|Corresponding Author||Wu，Changfeng; Chen，Qiang; Zhang，Xuanjun|
Photosensitizers to precise target and change fluorescence upon light illumination could accurately self-report where and when the photosensitizers work, enabling us to visualize the therapeutic process and precisely regulate treatment outcomes, which is the unremitting pursuit of precision and personalized medicine. Here, we report self-immolative photosensitizers by adopting a strategy of light-manipulated oxidative cleavage of C═C bonds that can generate a burst of reactive oxygen species, to cleave to release self-reported red-emitting products and trigger nonapoptotic cell oncosis. Strong electron-withdrawing groups are found to effectively suppress the C═C bond cleavage and phototoxicity via studying the structure-activity relationship, allowing us to elaborate NG1-NG5 that could temporarily inactivate the photosensitizer and quench the fluorescence by different glutathione (GSH)-responsive groups. Thereinto, NG2 with 2-cyano-4-nitrobenzene-1-sulfonyl group displays excellent GSH responsiveness than the other four. Surprisingly, NG2 shows better reactivity with GSH in weakly acidic condition, which inspires the application in weakly acidic tumor microenvironment where GSH elevates. To this end, we further synthesize NG-cRGD by anchoring integrin αβ binding cyclic pentapeptide (cRGD) for tumor targeting. In A549 xenografted tumor mice, NG-cRGD successfully deprotects to restore near-infrared fluorescence because of elevated GSH in tumor site, which is subsequently cleaved upon light irradiation releasing red-emitting products to report photosensitizer working, while effectively ablating tumors via triggered oncosis. The advanced self-immolative organic photosensitizer may accelerate the development of self-reported phototheranostics in future precision oncology.
NI Journal Papers ; NI论文
Science and Technology Development Fund, Macau SAR["0114/2019/A2","0085/2020/A2","0058/2022/A1","0087/2022/A2"] ; Guangdong Basic and Applied Basic Research Foundation["2022A1515010616","2023A1515012524"] ; Shenzhen Science and Technology Program["KQTD20170810111314625","JCYJ20210324115807021"] ; Research Grant of University of Macau["SRG2021-00008-FHS","MYRG2020-00130-FHS","MYRG2022-00036-FHS"]
|WOS Research Area|
|WOS Accession No|
Cited Times [WOS]:4
|Document Type||Journal Article|
|Department||Department of Biomedical Engineering|
1.Faculty of Health Sciences,University of Macau,999078,Macao
2.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,China
3.MOE Frontiers Science Centre for Precision Oncology,University of Macau,999078,Macao
|Corresponding Author Affilication||Department of Biomedical Engineering|
Wang，Chunfei,Sun，Yongjie,Huang，Shaojuan,et al. Self-Immolative Photosensitizers for Self-Reported Cancer Phototheranostics[J]. Journal of the American Chemical Society,2023,145(24):13099-13113.
Wang，Chunfei.,Sun，Yongjie.,Huang，Shaojuan.,Wei，Zixiang.,Tan，Jingyun.,...&Zhang，Xuanjun.(2023).Self-Immolative Photosensitizers for Self-Reported Cancer Phototheranostics.Journal of the American Chemical Society,145(24),13099-13113.
Wang，Chunfei,et al."Self-Immolative Photosensitizers for Self-Reported Cancer Phototheranostics".Journal of the American Chemical Society 145.24(2023):13099-13113.
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