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Cancer-Selective Bioreductive ChemotherapynMediated by Dual Hypoxia-Responsive Nanomedicine upon PhotodynamicnTherapy-Induced Hypoxia Aggravation 光动力疗法诱导的缺氧加重中，双低氧反应纳米药物介导的癌症选择性生物还原化疗

Figshare Pub Date : 2019-05-24 DOI: 10.1021/acs.biomac.9b00428.s001

Rongying Zhu (5955887), Hua He (120374), Yong Liu (6908), Desheng Cao (6822689), Jin Yan (193119), Shanzhou Duan (5955884), Yongbing Chen (5955890), Lichen Yin (1315224)

{"title":"Cancer-Selective Bioreductive ChemotherapynMediated by Dual Hypoxia-Responsive Nanomedicine upon PhotodynamicnTherapy-Induced Hypoxia Aggravation","authors":"Rongying Zhu (5955887), Hua He (120374), Yong Liu (6908), Desheng Cao (6822689), Jin Yan (193119), Shanzhou Duan (5955884), Yongbing Chen (5955890), Lichen Yin (1315224)","doi":"10.1021/acs.biomac.9b00428.s001","DOIUrl":"https://doi.org/10.1021/acs.biomac.9b00428.s001","url":null,"abstract":"Stimuli-responsivendrug delivery has rendered promising utilities in cancer treatment.nNevertheless, cancer selectivity as well as sensitivity still remainsncritical challenges that would undermine the therapeutic efficacynof chemodrugs and cause undesired systemic toxicity. Herein, a dualnhypoxia-responsive drug delivery system was developed to enable photodynamicntherapy (PDT)-induced drug release and drug activation intermediatednvia PDT-induced hypoxia. Particularly, tumor-targeting and hypoxia-dissociablennanoparticles (NPs) were self-assembled from the amphiphilic polyethylenimine–alkylnnitroimidazole [PEI–ANI, (PA)] and hyaluronic acid-chlorinne6 (HA-Ce6) to encapsulate bioreductive chemodrug, tirapazamine (TPZ).nAfter systemic administration, the obtained PA/HA-Ce6@TPZ NPs enabledneffective tumor accumulation due to HA-mediated cancer targeting.nUpon receptor-mediated endocytosis, light irradiation (660 nm, 10nmW/cm<sup>2</sup>) produced high levels of reactive oxygen speciesnto mediate PDT and generated a severe local hypoxic environment tondissociate the NPs and selectively release TPZ, as a consequence ofnhypoxia-triggered hydrophobic-to-hydrophilic transformation of ANI.nIn the meantime, TPZ was activated under hypoxia, finally contributingnto a synergistic anticancer treatment between PDT and hypoxia-strengthenednbioreductive chemotherapy. This study, therefore, demonstrates a suitablenstrategy for cancer-selective drug delivery as well as programmedncombination therapy.","PeriodicalId":522267,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147894356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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