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Phosphorus dendron nanomicelles as a platform for combination anti-inflammatory and antioxidative therapy of acute lung injury

2022Journal article Open access
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dc.contributor.authorLi, Jin
dc.contributor.authorChen, Liang
dc.contributor.authorLi, Changsheng
dc.contributor.authorFan, Yu
dc.contributor.authorZhan, Mengsi
dc.contributor.authorSun, Huxiao
dc.contributor.authorMignani, Serge
dc.contributor.authorMajoral, Jean-Pierre
dc.contributor.authorShen, Mingwu
dc.contributor.authorShi, Xiangyang
dc.date.accessioned2024-03-01T15:23:15Z
dc.date.available2024-03-01T15:23:15Z
dc.date.issued2022
dc.description.abstractRationale: Development of novel nanomedicines to inhibit pro-inflammatory cytokine expression and reactive oxygen species (ROS) generation for anti-inflammatory therapy of acute lung injury (ALI) remains challenging. Here, we present a new nanomedicine platform based on tyramine-bearing two dimethylphosphonate sodium salt (TBP)-modified amphiphilic phosphorus dendron (C11G3) nanomicelles encapsulated with antioxidant drug curcumin (Cur). Methods: C11G3-TBP dendrons were synthesized via divergent synthesis and self-assembled to generate nanomicelles in a water environment to load hydrophobic drug Cur. The created C11G3-TBP@Cur nanomicelles were well characterized and systematically examined in their cytotoxicity, cellular uptake, intracellular ROS elimination, pro-inflammatory cytokine inhibition and alveolar macrophages M2 type repolarization in vitro, and evaluated to assay their anti-inflammatory and antioxidative therapy effects of ALI mice model through pro-inflammatory cytokine expression level in bronchoalveolar lavage fluid and lung tissue, histological analysis and micro-CT imaging detection of lung tissue injury in vivo. Results: The nanomicelles with rigid phosphorous dendron structure enable high-capacity and stable Cur loading. Very strikingly, the drug-free C11G3-TBP micelles exhibit excellent cytocompatibility and intrinsic anti-inflammatory activity through inhibition of nuclear transcription factor-kappa B, thus causing repolarization of alveolar macrophages from M1 type to anti-inflammatory M2 type. Taken together with the strong ROS scavenging property of the encapsulated Cur, the developed nanomicelles enable effective therapy of inflammatory alveolar macrophages in vitro and an ALI mouse model in vivo after atomization administration. Conclusion: The created phosphorus dendron nanomicelles can be developed as a general nanomedicine platform for combination anti-inflammatory and antioxidative therapy of inflammatory diseases.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLi, J., Chen, L., Li, C., Fan, Y., Zhan, M., Sun, H., ... & Shi, X. (2022). Phosphorus dendron nanomicelles as a platform for combination anti-inflammatory and antioxidative therapy of acute lung injury. Theranostics, 12(7), 3407.pt_PT
dc.identifier.doi10.7150/thno.70701pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/5598
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherIvyspring International Publisherpt_PT
dc.relationMadeira Chemistry Research Centre
dc.relationMadeira Chemistry Research Centre
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectPhosphorus dendronspt_PT
dc.subjectNanomicellespt_PT
dc.subjectCurcuminpt_PT
dc.subjectAlveolar macrophagespt_PT
dc.subjectNF-κBpt_PT
dc.subjectAcute lung injurypt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.subjectCentro de Química da Madeira
dc.titlePhosphorus dendron nanomicelles as a platform for combination anti-inflammatory and antioxidative therapy of acute lung injurypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMadeira Chemistry Research Centre
oaire.awardTitleMadeira Chemistry Research Centre
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00674%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00674%2F2020/PT
oaire.citation.endPage3419pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage3407pt_PT
oaire.citation.titleTheranosticspt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameMignani
person.familyNameShen
person.familyNameShi
person.givenNameSerge
person.givenNameMingwu
person.givenNameXiangyang
person.identifier478951
person.identifier.ciencia-id8018-B5D2-6983
person.identifier.ciencia-idBA11-1437-B948
person.identifier.orcid0000-0002-1383-5256
person.identifier.orcid0000-0002-1065-0854
person.identifier.orcid0000-0001-6785-6645
person.identifier.ridA-1289-2007
person.identifier.scopus-author-id7003374430
person.identifier.scopus-author-id7402953116
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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