An all-in-one nanoparticle for overcoming drug resistance: doxorubicin and elacridar co-loaded folate receptor targeted PLGA/MSN hybrid nanoparticles

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dc.authoridŞahin, Adem/0000-0002-3996-2931
dc.authoridTonbul, Hayrettin/0000-0001-5510-8973
dc.authorwosidŞahin, Adem/IYT-0077-2023
dc.contributor.authorTonbul, Hayrettin
dc.contributor.authorSahin, Adem
dc.contributor.authorOzturk, Sueleyman Can
dc.contributor.authorUltav, Goezde
dc.contributor.authorTavukcuoglu, Ece
dc.contributor.authorAkbas, Sedenay
dc.contributor.authorAktas, Yesim
dc.date.accessioned2024-08-04T20:56:09Z
dc.date.available2024-08-04T20:56:09Z
dc.date.issued2024
dc.departmentİnönü Üniversitesien_US
dc.description.abstractOverexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. In vitro and in vivo studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, in vitro. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx (R)) or its combination with elacridar.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBITAK) Project [216S999]; Research Fund of the Inonu University Project [TCD-2021-2229]en_US
dc.description.sponsorshipThis work was supported by The Scientific and Technological Research Council of Turkiye (TUBITAK) Project Number: 216S999 and the Research Fund of the Inonu University Project Number: TCD-2021-2229.en_US
dc.identifier.doi10.1080/1061186X.2024.2374034
dc.identifier.issn1061-186X
dc.identifier.issn1029-2330
dc.identifier.pmid38946465en_US
dc.identifier.scopus2-s2.0-85197544608en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1080/1061186X.2024.2374034
dc.identifier.urihttps://hdl.handle.net/11616/102095
dc.identifier.wosWOS:001262754500001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Ltden_US
dc.relation.ispartofJournal of Drug Targetingen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectHybrid nanoparticlesen_US
dc.subjectdrug resistanceen_US
dc.subjectMDRen_US
dc.subjectP-gpen_US
dc.subjectelacridaren_US
dc.subjectdoxorubicinen_US
dc.titleAn all-in-one nanoparticle for overcoming drug resistance: doxorubicin and elacridar co-loaded folate receptor targeted PLGA/MSN hybrid nanoparticlesen_US
dc.typeArticleen_US

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