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NanoparticlesnEncapsulating Nitrosylated MaytansinenTo Enhance Radiation Therapy 纳米粒子封装亚硝基化美坦氨酸增强放射治疗

Figshare Pub Date : 2020-01-15 DOI: 10.1021/acsnano.9b05976.s001

Shi Gao (633889), Weizhong Zhang (170125), Renjie Wang (1986553), Sean P. Hopkins (3359498), Jonathan C. Spagnoli (8321907), Mohammed Racin (8321910), Lin Bai (338207), Lu Li (14069), Wen Jiang (274586), Xueyuan Yang (6311609), Chaebin Lee (8321913), Koichi Nagata (2084386), Elizabeth W. Howerth (7340246), Hitesh Handa (2302699), Jin Xie (690890), Qingjie Ma (633888), Anil Kumar (105720)

{"title":"NanoparticlesnEncapsulating Nitrosylated MaytansinenTo Enhance Radiation Therapy","authors":"Shi Gao (633889), Weizhong Zhang (170125), Renjie Wang (1986553), Sean P. Hopkins (3359498), Jonathan C. Spagnoli (8321907), Mohammed Racin (8321910), Lin Bai (338207), Lu Li (14069), Wen Jiang (274586), Xueyuan Yang (6311609), Chaebin Lee (8321913), Koichi Nagata (2084386), Elizabeth W. Howerth (7340246), Hitesh Handa (2302699), Jin Xie (690890), Qingjie Ma (633888), Anil Kumar (105720)","doi":"10.1021/acsnano.9b05976.s001","DOIUrl":"https://doi.org/10.1021/acsnano.9b05976.s001","url":null,"abstract":"Radiotherapynremains a major treatment modality for cancer typesnsuch as non-small cell lung carcinoma (or NSCLC). To enhance treatmentnefficacy at a given radiation dose, radiosensitizers are often usednduring radiotherapy. Herein, we report a nanoparticle agent that cannselectively sensitize cancer cells to radiotherapy. Specifically,nwe nitrosylated maytansinoid DM1 and then loaded the resulting prodrug,nDM1-NO, onto poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles.nThe toxicity of DM1 is suppressed by nanoparticle encapsulation andnnitrosylation, allowing the drug to be delivered to tumors throughnthe enhanced permeability and retention effect. Under irradiationnto tumors, the oxidative stress is elevated, leading to the cleavagenof the S–N bond and the release of DM1 and nitric oxide (NO).nDM1 inhibits microtubule polymerization and enriches cells at thenG2/M phase, which is more radiosensitive. NO under irradiation formsnhighly toxic radicals such as peroxynitrites, which also contributento tumor suppression. The two components work synergistically to enhancenradiotherapy outcomes, which was confirmed in vitro by clonogenic assays and in vivo with H1299 tumor-bearingnmice. Our studies suggest the great promise of DM1-NO PLGA nanoparticlesnin enhancing radiotherapy against NSCLC and potentially other tumorntypes.","PeriodicalId":521891,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147887466","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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