Orally Deliverable Nanotherapeutics for the Synergistic Treatment of Colitis-Associated Colorectal Cancer
Identifieur interne : 000568 ( Main/Exploration ); précédent : 000567; suivant : 000569Orally Deliverable Nanotherapeutics for the Synergistic Treatment of Colitis-Associated Colorectal Cancer
Auteurs : Weidong Han [République populaire de Chine] ; Binbin Xie [République populaire de Chine] ; Yiran Li [République populaire de Chine] ; Linlin Shi [République populaire de Chine] ; Jianqin Wan [République populaire de Chine] ; Xiaona Chen [République populaire de Chine] ; Hangxiang Wang [République populaire de Chine]Source :
- Theranostics [ 1838-7640 ] ; 2019.
Abstract
Results: The resulting amphiphilic constructs formed core-shell nanostructures in aqueous solutions and were orally administered for
Url:
DOI: 10.7150/thno.38081
PubMed: 31695780
PubMed Central: 6831307
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Orally Deliverable Nanotherapeutics for the Synergistic Treatment of Colitis-Associated Colorectal Cancer</title><author><name sortKey="Han, Weidong" sort="Han, Weidong" uniqKey="Han W" first="Weidong" last="Han">Weidong Han</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Xie, Binbin" sort="Xie, Binbin" uniqKey="Xie B" first="Binbin" last="Xie">Binbin Xie</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Li, Yiran" sort="Li, Yiran" uniqKey="Li Y" first="Yiran" last="Li">Yiran Li</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Shi, Linlin" sort="Shi, Linlin" uniqKey="Shi L" first="Linlin" last="Shi">Linlin Shi</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Wan, Jianqin" sort="Wan, Jianqin" uniqKey="Wan J" first="Jianqin" last="Wan">Jianqin Wan</name><affiliation wicri:level="4"><nlm:aff id="A2">The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Chen, Xiaona" sort="Chen, Xiaona" uniqKey="Chen X" first="Xiaona" last="Chen">Xiaona Chen</name><affiliation wicri:level="4"><nlm:aff id="A2">The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Wang, Hangxiang" sort="Wang, Hangxiang" uniqKey="Wang H" first="Hangxiang" last="Wang">Hangxiang Wang</name><affiliation wicri:level="4"><nlm:aff id="A2">The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31695780</idno><idno type="pmc">6831307</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831307</idno><idno type="RBID">PMC:6831307</idno><idno type="doi">10.7150/thno.38081</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000822</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000822</idno><idno type="wicri:Area/Pmc/Curation">000822</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000822</idno><idno type="wicri:Area/Pmc/Checkpoint">000519</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000519</idno><idno type="wicri:Area/Ncbi/Merge">000B79</idno><idno type="wicri:Area/Ncbi/Curation">000B79</idno><idno type="wicri:Area/Ncbi/Checkpoint">000B79</idno><idno type="wicri:Area/Main/Merge">000568</idno><idno type="wicri:Area/Main/Curation">000568</idno><idno type="wicri:Area/Main/Exploration">000568</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Orally Deliverable Nanotherapeutics for the Synergistic Treatment of Colitis-Associated Colorectal Cancer</title><author><name sortKey="Han, Weidong" sort="Han, Weidong" uniqKey="Han W" first="Weidong" last="Han">Weidong Han</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Xie, Binbin" sort="Xie, Binbin" uniqKey="Xie B" first="Binbin" last="Xie">Binbin Xie</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Li, Yiran" sort="Li, Yiran" uniqKey="Li Y" first="Yiran" last="Li">Yiran Li</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Shi, Linlin" sort="Shi, Linlin" uniqKey="Shi L" first="Linlin" last="Shi">Linlin Shi</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine, Zhejiang University, Hangzhou, 310016</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Wan, Jianqin" sort="Wan, Jianqin" uniqKey="Wan J" first="Jianqin" last="Wan">Jianqin Wan</name><affiliation wicri:level="4"><nlm:aff id="A2">The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Chen, Xiaona" sort="Chen, Xiaona" uniqKey="Chen X" first="Xiaona" last="Chen">Xiaona Chen</name><affiliation wicri:level="4"><nlm:aff id="A2">The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Wang, Hangxiang" sort="Wang, Hangxiang" uniqKey="Wang H" first="Hangxiang" last="Wang">Hangxiang Wang</name><affiliation wicri:level="4"><nlm:aff id="A2">The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003, PR China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The First Affiliated Hospital; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; School of Medicine, Zhejiang University, Hangzhou, 310003</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author></analytic><series><title level="j">Theranostics</title><idno type="eISSN">1838-7640</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Purpose:</bold> Colitis-associated colorectal cancer (CAC) poses substantial challenges for effective treatment. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the safe and effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract.</p><p><bold>Experimental Design:</bold> In this study, we developed orally deliverable nanotherapeutics for the synergistic treatment of inflammatory bowel diseases (IBDs) and CAC. Water-insoluble curcumin (CUR) and 7-ethyl-10-hydroxycamptothecin (SN38), which served as anti-inflammatory and cytotoxic agents, respectively, were chemically engineered into hydrophilic mucoadhesive chitosan for the generation of chitosan-drug amphiphiles.</p><p>Results: The resulting amphiphilic constructs formed core-shell nanostructures in aqueous solutions and were orally administered for <italic>in vivo</italic> therapeutic studies. Using a preclinical CAC mouse model, we showed that the orally delivered nanotherapeutics locally accumulated in inflamed intestinal regions and tumor tissues. Furthermore, the therapeutic synergy of the combined nanotherapeutics in CAC mice was evaluated. Compared with their individual drug forms, combined CUR and SN38 nanoparticles yielded synergistic effects to alleviate intestinal inflammation and protect mice from ulcerative colitis. Notably, the combinatorial therapy demonstrated a remarkable tumor shrinkage with only ~6% of the total tumors exceeding 4 mm in diameter, whereas ~35% of tumors were observed to exceed a diameter of 4 mm in the saline-treated CAC mice. These data suggest a new and reliable approach for improving the treatment of IBD and CAC.</p><p><bold>Conclusions:</bold> Our results showed that bioadhesive chitosan materials can be used to produce colloidal-stable nanotherapeutics that are suitable for oral delivery. Both nanotherapeutics exhibited substantial accumulation in inflamed intestinal regions and tumor tissues and showed good synergy for treating CAC, warranting further clinical translation.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cunningham, D" uniqKey="Cunningham D">D Cunningham</name></author><author><name sortKey="Atkin, W" uniqKey="Atkin W">W Atkin</name></author><author><name sortKey="Lenz, Hj" uniqKey="Lenz H">HJ Lenz</name></author><author><name sortKey="Lynch, Ht" uniqKey="Lynch H">HT Lynch</name></author><author><name sortKey="Minsky, B" uniqKey="Minsky B">B Minsky</name></author><author><name sortKey="Nordlinger, B" uniqKey="Nordlinger B">B Nordlinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siegel, Rl" uniqKey="Siegel R">RL Siegel</name></author><author><name sortKey="Miller, Kd" uniqKey="Miller K">KD Miller</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal 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Y" first="Yiran" last="Li">Yiran Li</name><name sortKey="Shi, Linlin" sort="Shi, Linlin" uniqKey="Shi L" first="Linlin" last="Shi">Linlin Shi</name><name sortKey="Wan, Jianqin" sort="Wan, Jianqin" uniqKey="Wan J" first="Jianqin" last="Wan">Jianqin Wan</name><name sortKey="Wang, Hangxiang" sort="Wang, Hangxiang" uniqKey="Wang H" first="Hangxiang" last="Wang">Hangxiang Wang</name><name sortKey="Xie, Binbin" sort="Xie, Binbin" uniqKey="Xie B" first="Binbin" last="Xie">Binbin Xie</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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