{"title":"用于可激活光动力疗法的 pH 响应型自组装聚合物-光敏剂共轭物","authors":"Tanushri Banerjee, Krishna Dan, Suhrit Ghosh","doi":"10.1039/d4nr03249g","DOIUrl":null,"url":null,"abstract":"This paper reports synthesis, aqueous self-assembly and relevance in the pH-triggered activable photodynamic therapy of an amphiphilic polyurethane (P1S), functionalized with a heavy-atom free organic photosensitizer. Condensation polymerization between 1,4-diisocyanatobutane and two different dihydroxy monomers (one having pendant hydrophilic wedge and the other having 1,3-dihydroxypropan-2-one with a reactive carbonyl-group) in presence of measured amount of (S)-2-methylbutan-1-ol (chain-stopper) and DABCO catalyst produces the reactive pre-polymer P1. Hydrazide- functionalized thionated-naphthalenemonimide (NMIS), that acts as a photosensitizer, was reacted with the carbonyl-functionality of P1 to get the desired polymer-photosensitizer conjugate P1S in which the dye was attached to the polymer backbone by the acid-labile hydrazone linker. In water, P1S adopted intra-chain H-bonding stabilized folded structure, which further assembled to produce polymersome structure (Dh ~ 200 nm), in which the hydrophobic membrane consists of aggregated NMIS and trialkoxy-benzene chromophores, as evident from the UV/Vis, CD and small-angle X-ray diffraction studies. In the aggregated state, the NMIS loses its reactive oxygen species (ROS)-generation ability and remains in the dormant state. However, in acidic condition (pH 5.5), the photosensitizer is detached (presumably due to the cleavage of the hydrazone-linker) and regains its full ROS-generation activity under photoirradiation, as evidenced from the standard DCFH assay. To test the possibility of such pH-activable intra-cellular ROS generation, P1S was treated with HeLa cells as it is known that cancer cells are more acidic than normal cells. Indeed, photoirradiation induced intra-cellular ROS generation was evident by the DCFH assay, resulting in efficient cell killing.","PeriodicalId":92,"journal":{"name":"Nanoscale","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"pH-Responsive Self-assembled Polymer-Photosensitizer Conjugate for Activable Photodynamic Therapy\",\"authors\":\"Tanushri Banerjee, Krishna Dan, Suhrit Ghosh\",\"doi\":\"10.1039/d4nr03249g\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"This paper reports synthesis, aqueous self-assembly and relevance in the pH-triggered activable photodynamic therapy of an amphiphilic polyurethane (P1S), functionalized with a heavy-atom free organic photosensitizer. Condensation polymerization between 1,4-diisocyanatobutane and two different dihydroxy monomers (one having pendant hydrophilic wedge and the other having 1,3-dihydroxypropan-2-one with a reactive carbonyl-group) in presence of measured amount of (S)-2-methylbutan-1-ol (chain-stopper) and DABCO catalyst produces the reactive pre-polymer P1. Hydrazide- functionalized thionated-naphthalenemonimide (NMIS), that acts as a photosensitizer, was reacted with the carbonyl-functionality of P1 to get the desired polymer-photosensitizer conjugate P1S in which the dye was attached to the polymer backbone by the acid-labile hydrazone linker. In water, P1S adopted intra-chain H-bonding stabilized folded structure, which further assembled to produce polymersome structure (Dh ~ 200 nm), in which the hydrophobic membrane consists of aggregated NMIS and trialkoxy-benzene chromophores, as evident from the UV/Vis, CD and small-angle X-ray diffraction studies. In the aggregated state, the NMIS loses its reactive oxygen species (ROS)-generation ability and remains in the dormant state. However, in acidic condition (pH 5.5), the photosensitizer is detached (presumably due to the cleavage of the hydrazone-linker) and regains its full ROS-generation activity under photoirradiation, as evidenced from the standard DCFH assay. To test the possibility of such pH-activable intra-cellular ROS generation, P1S was treated with HeLa cells as it is known that cancer cells are more acidic than normal cells. Indeed, photoirradiation induced intra-cellular ROS generation was evident by the DCFH assay, resulting in efficient cell killing.\",\"PeriodicalId\":92,\"journal\":{\"name\":\"Nanoscale\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanoscale\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1039/d4nr03249g\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanoscale","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1039/d4nr03249g","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
pH-Responsive Self-assembled Polymer-Photosensitizer Conjugate for Activable Photodynamic Therapy
This paper reports synthesis, aqueous self-assembly and relevance in the pH-triggered activable photodynamic therapy of an amphiphilic polyurethane (P1S), functionalized with a heavy-atom free organic photosensitizer. Condensation polymerization between 1,4-diisocyanatobutane and two different dihydroxy monomers (one having pendant hydrophilic wedge and the other having 1,3-dihydroxypropan-2-one with a reactive carbonyl-group) in presence of measured amount of (S)-2-methylbutan-1-ol (chain-stopper) and DABCO catalyst produces the reactive pre-polymer P1. Hydrazide- functionalized thionated-naphthalenemonimide (NMIS), that acts as a photosensitizer, was reacted with the carbonyl-functionality of P1 to get the desired polymer-photosensitizer conjugate P1S in which the dye was attached to the polymer backbone by the acid-labile hydrazone linker. In water, P1S adopted intra-chain H-bonding stabilized folded structure, which further assembled to produce polymersome structure (Dh ~ 200 nm), in which the hydrophobic membrane consists of aggregated NMIS and trialkoxy-benzene chromophores, as evident from the UV/Vis, CD and small-angle X-ray diffraction studies. In the aggregated state, the NMIS loses its reactive oxygen species (ROS)-generation ability and remains in the dormant state. However, in acidic condition (pH 5.5), the photosensitizer is detached (presumably due to the cleavage of the hydrazone-linker) and regains its full ROS-generation activity under photoirradiation, as evidenced from the standard DCFH assay. To test the possibility of such pH-activable intra-cellular ROS generation, P1S was treated with HeLa cells as it is known that cancer cells are more acidic than normal cells. Indeed, photoirradiation induced intra-cellular ROS generation was evident by the DCFH assay, resulting in efficient cell killing.
期刊介绍:
Nanoscale is a high-impact international journal, publishing high-quality research across nanoscience and nanotechnology. Nanoscale publishes a full mix of research articles on experimental and theoretical work, including reviews, communications, and full papers.Highly interdisciplinary, this journal appeals to scientists, researchers and professionals interested in nanoscience and nanotechnology, quantum materials and quantum technology, including the areas of physics, chemistry, biology, medicine, materials, energy/environment, information technology, detection science, healthcare and drug discovery, and electronics.