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Self‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cells

2021Journal article Open access
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dc.contributor.authorOlim, Filipe
dc.contributor.authorNeves, Ana Rute
dc.contributor.authorVieira, Mariana
dc.contributor.authorTomás, Helena
dc.contributor.authorSheng, Ruilong
dc.date.accessioned2021-11-16T15:05:33Z
dc.date.available2021-11-16T15:05:33Z
dc.date.issued2021
dc.description.abstractDeveloping new easy-to-prepare functional drug delivery nanosystems with good storage stability, low hemotoxicity, as well as controllable drug delivery property, has attracted great attention in recent years. In this work, a cholesterol-based prodrug nanodelivery system is prepared by self-assembly of cholesterol-doxorubicin prodrug conjugates (Chol-Dox) and tocopherol polyethylene glycol succinate (TPGS) using thin-film hydration method. The Chol-Dox/TPGS assemblies (molar ratio 2:1, 1:1, and 1:2) are able to form nanoparticles with average hydrodynamic diameter of ≈140–214 nm, surface zeta potentials of ≈−24.2–−0.3 mV, and remarkable solution stability in 0.1 m PBS, 16 days). The Chol-Dox/TPGS assemblies show low hemotoxicity and different cytotoxicity profiles in breast cancer cells (MCF-7 and MDA-MB-231), which are largely dependent on the molar ratio of Chol-Dox and TPGS. The Chol-Dox/TPGS assemblies tend to enter into MCF-7 and MDA-MB-231 cells through non-Clathrin-mediated multiple endocytosis and lysosome-dependent uptake pathways, moreover, these nanoassemblies demonstrate lysosome-dependent intracellular localization, which is different from that of free DOX (nuclear localization). The results demonstrate that the Chol-Dox/TPGS assemblies are promising cholesterol-based prodrug nanomaterials for breast cancer chemotherapy. Practical Applications: This work demonstrates a lipid prodrug-based nanotherapeutic system. Herein the Chol-Dox/TPGS nanoassemblies could serve as promising and controllable cholesterol-based prodrug nanomaterials/nano-formulations for potential breast cancer chemotherapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationOlim, F., Neves, A. R., Vieira, M., Tomás, H., & Sheng, R. (2021). Self‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cells. European Journal of Lipid Science and Technology, 123(5), 2000337. https://doi.org/10.1002/ejlt.202000337pt_PT
dc.identifier.doi10.1002/ejlt.202000337pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/3822
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationMadeira Chemistry Research Centre
dc.relationMadeira Chemistry Research Centre
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectSelf-assembly of cholesterol-doxorubicinpt_PT
dc.subjectProdrug-based nanoparticlespt_PT
dc.subjectEnhanced cellular uptakept_PT
dc.subjectLysosome-dependentpt_PT
dc.subjectBreast cancer cellspt_PT
dc.subjectCholesterol-doxorubicinpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.subjectCentro de Química da Madeira
dc.titleSelf‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cellspt_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.issue5pt_PT
oaire.citation.startPage2000337pt_PT
oaire.citation.titleEuropean Journal of Lipid Science and Technologypt_PT
oaire.citation.volume123pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameOlim
person.familyNameNeves
person.familyNameCatanho da Silva Vieira
person.familyNameTomás
person.familyNameSheng
person.givenNameFilipe
person.givenNameAna Rute
person.givenNameMariana
person.givenNameHelena
person.givenNameRuilong
person.identifier556975
person.identifierhttps://scholar.google.ca/citations?user=YCheaFsAAAAJ&hl=en
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person.identifier.ciencia-idC019-C809-403B
person.identifier.orcid0000-0001-8878-2067
person.identifier.orcid0000-0003-4262-5837
person.identifier.orcid0000-0001-5928-4237
person.identifier.orcid0000-0002-7856-2041
person.identifier.orcid0000-0002-3303-3832
person.identifier.ridO-6395-2018
person.identifier.ridH-3743-2013
person.identifier.ridE-5991-2010
person.identifier.scopus-author-id56731303900
person.identifier.scopus-author-id6508104177
person.identifier.scopus-author-id7005472737
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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