In Vitro Assessment of 177Lu-labeled Trastuzumab-Targeted Mesoporous Carbon@Silica Nanostructure for the treatment of HER2-Positive Breast Cancer
Diğer yayınlar > Diğer · 2023
Yazarlar: Ayça Tunçel, Simone Maschauer, Olaf Prante, Fatma YURT
Diğer, Uluslararası, 2023,
Özet
Abstract Background: This study evaluated the in vitro efficacy of 177Lu-labeled mesoporous Carbon@Silica nanostructure targeted with trastuzumab (TRA/PEI-MC@Si). This study aimed to explore the potential of TRA/PEI-MC@Si as a targeted radiotherapeutic for the treatment of HER2-positive breast cancer, with a focus on understanding its cellular uptake, internalization, and efflux capacity on various cell lines. Results: The TRA/PEI-MC@Si nanocomposite was successfully labeled with 177Lu, yielding a radiochemical yield of 93.0±2.4%. In vitro studies revealed a higher uptake of the 177Lu-DOTA@TRA/MC@Si nanocomposite in HER2-positive SK-BR-3 cells (44.0±4.6% within the first 24 hours) compared to MDA-MB-231 cells (21.0±2.3%). The IC50 values for SK-BR-3 and MDA-MB-231 were 0.17 nM and 0.09 M, respectively, indicating a higher affinity towards HER-2 receptor-expressing cells. The lipophilic distribution coefficients of the radiolabeled nanocomposites were determined to be 1.7±0.3 for 177Lu-DOTA@TRA/MC@Si and 1.5±0.2 for 177Lu-DOTA@PEI-MC@Si, suggesting sufficient passive transport through the cell membrane and increased accumulation in target tissues. Conclusions: The 177Lu-TRA@DOTA/PEI-MC@Si nanocomposite demonstrated significant targeting efficacy towards HER2-positive cell lines, showing promise as a potential therapeutic agent for the treatment and nuclear imaging of HER2-positive breast cancer. The findings suggest that the TRA-targeted DOTA@PEI-MC@Si nanocomposite, when labeled with Lu-177, could serve as an effective single-platform agent for the therapy of breast cancer.