{"title":"Acid-activatable photosensitizers for photodynamic therapy using self-aggregates of chlorophyll‒peptide conjugates","authors":"Miyu Nagatani, Masaru Yoshikawa, Shinya Tsukiji, Masahiro Higuchi, Hitoshi Tamiaki, Shogo Matsubara","doi":"10.1038/s41428-024-00961-2","DOIUrl":null,"url":null,"abstract":"<p>Photodynamic therapy is useful due to its high antitumor efficacy, spatiotemporal selectivity, and noninvasiveness and has garnered significant attention in the field of cancer treatment. When photoexcited by light irradiation, photosensitizers produce reactive oxygen species (ROS) that damage tumor tissues. However, photosensitizers can also accumulate in normal tissues, leading to side effects such as skin photosensitivity. To mitigate these side effects, we report the development of chlorophyll‒peptide conjugates as tumor-selective photosensitizers. These conjugates bearing histidine and lysine residues self-assemble into nanoparticles that are expected to accumulate selectively in tumors and reduce ROS generation through self-quenching under the neutral conditions typical of normal tissues. In contrast, these aggregated conjugates partially disassemble under weakly acidic conditions, such as those found in tumor tissues, resulting in phototoxicity. We anticipate that these acid-activatable conjugates have the potential to serve as cancer-selective photosensitizers, thereby reducing phototoxicity in normal tissues.</p>","PeriodicalId":20302,"journal":{"name":"Polymer Journal","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Polymer Journal","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1038/s41428-024-00961-2","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"POLYMER SCIENCE","Score":null,"Total":0}
引用次数: 0
Abstract
Photodynamic therapy is useful due to its high antitumor efficacy, spatiotemporal selectivity, and noninvasiveness and has garnered significant attention in the field of cancer treatment. When photoexcited by light irradiation, photosensitizers produce reactive oxygen species (ROS) that damage tumor tissues. However, photosensitizers can also accumulate in normal tissues, leading to side effects such as skin photosensitivity. To mitigate these side effects, we report the development of chlorophyll‒peptide conjugates as tumor-selective photosensitizers. These conjugates bearing histidine and lysine residues self-assemble into nanoparticles that are expected to accumulate selectively in tumors and reduce ROS generation through self-quenching under the neutral conditions typical of normal tissues. In contrast, these aggregated conjugates partially disassemble under weakly acidic conditions, such as those found in tumor tissues, resulting in phototoxicity. We anticipate that these acid-activatable conjugates have the potential to serve as cancer-selective photosensitizers, thereby reducing phototoxicity in normal tissues.
期刊介绍:
Polymer Journal promotes research from all aspects of polymer science from anywhere in the world and aims to provide an integrated platform for scientific communication that assists the advancement of polymer science and related fields. The journal publishes Original Articles, Notes, Short Communications and Reviews.
Subject areas and topics of particular interest within the journal''s scope include, but are not limited to, those listed below:
Polymer synthesis and reactions
Polymer structures
Physical properties of polymers
Polymer surface and interfaces
Functional polymers
Supramolecular polymers
Self-assembled materials
Biopolymers and bio-related polymer materials
Polymer engineering.