In Vitro Assessment of 177Lu-Labeled Trastuzumab-Targeted Mesoporous Carbon@Silica Nanostructure for the Treatment of HER2-Positive Breast Cancer

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dc.authoridMaschauer, Simone/0000-0002-6550-933X
dc.contributor.authorTuncel, Ayca
dc.contributor.authorMaschauer, Simone
dc.contributor.authorPrante, Olaf
dc.contributor.authorYurt, Fatma
dc.date.accessioned2024-08-31T07:49:38Z
dc.date.available2024-08-31T07:49:38Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractThis study assessed the effectiveness of a trastuzumab-targeted Lu-177-labeled mesoporous Carbon@Silica nanostructure (DOTA@TRA/MC@Si) for HER2-positive breast cancer treatment, focusing on its uptake, internalization, and efflux in breast cancer cells. The synthesized PEI-MC@Si nanocomposite was reacted with DOTA-NHS-ester, confirmed by the Arsenazo(III) assay. Following this, TRA was conjugated to the DOTA@PEI-MC@Si for targeting. DOTA@PEI-MC@Si and DOTA@TRA/MC@Si nanocomposites were labeled with Lu-177, and their efficacy was evaluated through in vitro radiolabeling experiments. According to the results, the DOTA@TRA/MC@Si nanocomposite was successfully labeled with Lu-177, yielding a radiochemical yield of 93.0 +/- 2.4%. In vitro studies revealed a higher uptake of the [Lu-177]Lu-DOTA@TRA/MC@Si nanocomposite in HER2-positive SK-BR-3 cells (44.0 +/- 4.6% after 24 h) compared to MDA-MB-231 cells (21.0 +/- 2.3%). The IC50 values for TRA-dependent uptake in the SK-BR-3 and BT-474 cells were 0.9 mu M and 1.3 mu M, respectively, indicating affinity toward HER-2 receptor-expressing cells. The lipophilic distribution coefficients of the radiolabeled nanocomposites were determined to be 1.7 +/- 0.3 for [Lu-177]Lu-DOTA@TRA/MC@Si and 1.5 +/- 0.2 for [Lu-177]Lu-DOTA@PEI-MC@Si, suggesting sufficient passive transport through the cell membrane and increased accumulation in target tissues. The [Lu-177]Lu-DOTA@TRA/MC@Si nanocomposite showed an uptake into HER2-positive cell lines, marking a valuable step toward the development of a nanoparticle-based therapeutic agent for an improved treatment strategy for HER2-positive breast cancer.en_US
dc.description.sponsorshipEge University BAP Commision [FDK21380]; TUBITAK 2214-A scholarshipen_US
dc.description.sponsorshipThis research was supported by the Ege University BAP Commision (project number FDK21380). A.T. was supported by a TUBITAK 2214-A scholarship.en_US
dc.identifier.doi10.3390/ph17060732
dc.identifier.issn1424-8247
dc.identifier.issue6en_US
dc.identifier.pmid38931400en_US
dc.identifier.scopus2-s2.0-85197206378en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3390/ph17060732
dc.identifier.urihttps://hdl.handle.net/11454/104922
dc.identifier.volume17en_US
dc.identifier.wosWOS:001257248000001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofPharmaceuticalsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240831_Uen_US
dc.subjectLu-177en_US
dc.subjectMesoporous Carbon And Silica Nanomaterialsen_US
dc.subjectHer2+ Breast Canceren_US
dc.subjectRadiolabelingen_US
dc.titleIn Vitro Assessment of 177Lu-Labeled Trastuzumab-Targeted Mesoporous Carbon@Silica Nanostructure for the Treatment of HER2-Positive Breast Canceren_US
dc.typeArticleen_US

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