{"title":"Effective disruption of cancer cell membranes by photodynamic therapy with cell membrane-adhesive photosensitizer.","authors":"Aoi Hoshi, Toru Yoshitomi, Yoshiki Komatsu, Naoki Kawazoe, Guoping Chen, Hiroko Bando, Hisato Hara, Hirofumi Matsui","doi":"10.3164/jcbn.24-88","DOIUrl":null,"url":null,"abstract":"<p><p>Photodynamic therapy (PDT) is a noninvasive cancer treatment modality that involves the administration of photosensitizers and light irradiation. Previously, we established a polycation-containing hematoporphyrin (aHP) formulation that demonstrated superior antitumor efficacy <i>in vivo</i>, than the original hematoporphyrin (HP). In this study, we investigated underlining mechanisms of the high antitumor effect of aHP using cell experiments. Time-lapse imaging of rat gastric cancerous cell line (RGK45) treated with aHP exhibited swelling, cell rupture, and subsequent scattering of small vesicles upon light irradiation, in contrast to the small changes in morphology of RGK45 treated with HP. Furthermore, aHP presented concentrated localization on the cell membranes to a greater extent than HP. Additionally, neither aHP nor HP induced morphological changes in rat gastric mucosa cell line (RGM1). Flow cytometry analysis demonstrated a higher fluorescence of wheat germ agglutinin-conjugated dye in RGK45 than in RGM1, suggesting differential glycan expression patterns. These findings collectively suggest that the cellular toxicity of aHP may be augmented in RGK45 cells owing to its heightened affinity toward negatively charged structures on cellular membranes and its preferential localization on them. The observed membrane rupture and release of extracellular vesicles may confer an abscopal effect, in addition to direct PDT effect, thereby positioning aHP as a promising next-generation photosensitizer.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"75 3","pages":"197-203"},"PeriodicalIF":2.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579852/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Biochemistry and Nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3164/jcbn.24-88","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/24 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Photodynamic therapy (PDT) is a noninvasive cancer treatment modality that involves the administration of photosensitizers and light irradiation. Previously, we established a polycation-containing hematoporphyrin (aHP) formulation that demonstrated superior antitumor efficacy in vivo, than the original hematoporphyrin (HP). In this study, we investigated underlining mechanisms of the high antitumor effect of aHP using cell experiments. Time-lapse imaging of rat gastric cancerous cell line (RGK45) treated with aHP exhibited swelling, cell rupture, and subsequent scattering of small vesicles upon light irradiation, in contrast to the small changes in morphology of RGK45 treated with HP. Furthermore, aHP presented concentrated localization on the cell membranes to a greater extent than HP. Additionally, neither aHP nor HP induced morphological changes in rat gastric mucosa cell line (RGM1). Flow cytometry analysis demonstrated a higher fluorescence of wheat germ agglutinin-conjugated dye in RGK45 than in RGM1, suggesting differential glycan expression patterns. These findings collectively suggest that the cellular toxicity of aHP may be augmented in RGK45 cells owing to its heightened affinity toward negatively charged structures on cellular membranes and its preferential localization on them. The observed membrane rupture and release of extracellular vesicles may confer an abscopal effect, in addition to direct PDT effect, thereby positioning aHP as a promising next-generation photosensitizer.
期刊介绍:
Journal of Clinical Biochemistry and Nutrition (JCBN) is
an international, interdisciplinary publication encompassing
chemical, biochemical, physiological, pathological, toxicological and medical approaches to research on lipid peroxidation, free radicals, oxidative stress and nutrition. The
Journal welcomes original contributions dealing with all
aspects of clinical biochemistry and clinical nutrition
including both in vitro and in vivo studies.