In Vitro Assessment of 177Lu-Labeled Trastuzumab-Targeted Mesoporous Carbon@Silica Nanostructure for the Treatment of HER2-Positive Breast Cancer
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Mdpi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
This 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.
Açıklama
Anahtar Kelimeler
Lu-177, Mesoporous Carbon And Silica Nanomaterials, Her2+ Breast Cancer, Radiolabeling
Kaynak
Pharmaceuticals
WoS Q Değeri
N/A
Scopus Q Değeri
Q1
Cilt
17
Sayı
6
