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Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

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dc.abstract.enModification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorBilewicz, Renata
dc.contributor.authorStępkowski, Tomasz
dc.contributor.authorMęczyńska-Wielgosz, Sylwia
dc.contributor.authorDzwonek, Maciej
dc.contributor.authorWięckowska, Agnieszka
dc.contributor.authorKruszewski, Marcin
dc.contributor.authorPiątek, Piotr
dc.contributor.authorZałubiniak, Dominika
dc.contributor.authorCichowicz, Grzegorz
dc.date.accessioned2024-01-26T11:03:46Z
dc.date.available2024-01-26T11:03:46Z
dc.date.copyright2018-04-19
dc.date.issued2018
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number27
dc.description.versionFINAL_PUBLISHED
dc.description.volume8
dc.identifier.doi10.1039/C8RA01107A
dc.identifier.issn2046-2069
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/123558
dc.identifier.weblinkhttps://pubs.rsc.org/en/content/articlelanding/2018/RA/C8RA01107A#!divAbstract
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofRSC Advances
dc.relation.pages14947-14957
dc.rightsCC-BY
dc.sciencecloudnosend
dc.titleTowards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit
dc.typeJournalArticle
dspace.entity.typePublication