{"title":"Hypoxia-triggered photothermal/drug combination therapy of tumors using a perylene diimide molecular capsule","authors":"Fei Yang, Guo Wang, Kecheng Huang, Yanqing Xu, Xiao Feng, Weizhi Wang, Wei Wei","doi":"10.1007/s11426-024-2231-1","DOIUrl":null,"url":null,"abstract":"<p>Hypoxia is a common characteristic of tumors and associated with poor outcome in most cancer types, thus hypoxia-triggered combined therapeutic systems with well-defined structure hold significant promise for achieving specific and effective tumor destruction. Herein, a water-soluble perylene diimide (PDI) cyclophane “Gemini Box” (<b>GBox-1</b><sup><b>4+</b></sup>) is demonstrated as both a hypoxia-responsive photothermal agent and a drug capsule for tumor-specific combination therapy. First, owing to the covalent enclosure of PDI chromophore by double-sided molecular straps, <b>GBox-1</b><sup><b>4+</b></sup> can significantly stabilize labile PDI radical anions generated through bioreduction at the lesion site of hypoxic tumors, leading to high-efficiency near-infrared photothermal ablation of tumors. Meanwhile, <b>GBox-1</b><sup><b>4+</b></sup> can act as a molecular capsule to bind water-insoluble antitumor drugs camptothecin and hydroxycamptothecin in 1:1 host–guest stoichiometry with high affinities, greatly enhancing the water solubility of drugs. Eventually, such drug-loading cyclophane system as a hypoxia-activated photothermal/drug combined therapeutic platform exhibits more effective inhibition of tumor growth than the single treatment under identical conditions. This study significantly extends the application range of host–guest cyclophane systems and opens a promising avenue to structurally uniform combined therapeutic agents against hypoxic tumors with improved specificity.</p>","PeriodicalId":772,"journal":{"name":"Science China Chemistry","volume":null,"pages":null},"PeriodicalIF":10.4000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science China Chemistry","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1007/s11426-024-2231-1","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Hypoxia is a common characteristic of tumors and associated with poor outcome in most cancer types, thus hypoxia-triggered combined therapeutic systems with well-defined structure hold significant promise for achieving specific and effective tumor destruction. Herein, a water-soluble perylene diimide (PDI) cyclophane “Gemini Box” (GBox-14+) is demonstrated as both a hypoxia-responsive photothermal agent and a drug capsule for tumor-specific combination therapy. First, owing to the covalent enclosure of PDI chromophore by double-sided molecular straps, GBox-14+ can significantly stabilize labile PDI radical anions generated through bioreduction at the lesion site of hypoxic tumors, leading to high-efficiency near-infrared photothermal ablation of tumors. Meanwhile, GBox-14+ can act as a molecular capsule to bind water-insoluble antitumor drugs camptothecin and hydroxycamptothecin in 1:1 host–guest stoichiometry with high affinities, greatly enhancing the water solubility of drugs. Eventually, such drug-loading cyclophane system as a hypoxia-activated photothermal/drug combined therapeutic platform exhibits more effective inhibition of tumor growth than the single treatment under identical conditions. This study significantly extends the application range of host–guest cyclophane systems and opens a promising avenue to structurally uniform combined therapeutic agents against hypoxic tumors with improved specificity.
期刊介绍:
Science China Chemistry, co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China and published by Science China Press, publishes high-quality original research in both basic and applied chemistry. Indexed by Science Citation Index, it is a premier academic journal in the field.
Categories of articles include:
Highlights. Brief summaries and scholarly comments on recent research achievements in any field of chemistry.
Perspectives. Concise reports on thelatest chemistry trends of interest to scientists worldwide, including discussions of research breakthroughs and interpretations of important science and funding policies.
Reviews. In-depth summaries of representative results and achievements of the past 5–10 years in selected topics based on or closely related to the research expertise of the authors, providing a thorough assessment of the significance, current status, and future research directions of the field.