Tuncel, AycaMaschauer, SimonePrante, OlafYurt, Fatma2024-08-312024-08-3120241424-8247https://doi.org/10.3390/ph17060732https://hdl.handle.net/11454/104922This 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.en10.3390/ph17060732info:eu-repo/semantics/openAccessLu-177Mesoporous Carbon And Silica NanomaterialsHer2+ Breast CancerRadiolabelingArticle176WOS:0012572480000012-s2.0-8519720637838931400Q1N/A