将多柔比星(DOX)-吉西他滨(GEM)金复合物纳米载体作为加列汀-1 生物标记物诊断工具的光谱学评估

Memona Khan, Khaoula Cherni, Rawdha Dekhili, J. Spadavecchia
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摘要

引言 本研究的目的是开发基于金-多柔比星(DOX)-吉西他滨(GEM)复合物的治疗杂交纳米载体,并将其与作为癌症治疗和预后标志物的Galectin-1(Gal-1)积极靶向。为此,金盐(HAuCl4)通过螯合作用与抗肿瘤药物(DOX;GEM)相互作用,然后用二羧酸封端聚乙二醇(PEG)作为生物相容性表面活性剂使其稳定。所提出的方法快速、可重复,并形成了一种名为 GEM@DOX IN PEG-AuNPs 的混合纳米载体,其化学生物稳定性得到了提高。使用各种光谱技术(拉曼光谱和紫外可见光谱)和透射电子显微镜(TEM)对所有合成化学产品进行了评估。结果 为了设想治疗应用,我们的混合纳米载体(GEM@DOX IN PEG-AuNPs)与不同浓度的 Galectin-1 蛋白(Gal-1)共轭,以预测和特异性识别癌细胞。SPR 和拉曼测量结果表明,Gal-1 与 PEG-AuNPs 中的 GEM@DOX 相互作用。我们观察到等离子体位置(SPR)和拉曼光谱带随 Gal-1 浓度的动态变化。讨论 我们发现,静电接枝到 DOX IN PEG-AuNPs 上的 GEM 具有更好的化学构象,其中氨基(NH3+)与 PEG 二酰羧基(COO-)反应,而 C-5' 位的环戊醇基则与 DOX 的 NH3+ 反应。结论 这项研究为制造 "智能纳米医疗设备 "开辟了新的道路,这种设备可以在纳米医学领域和临床前研究中发挥治疗和诊断的双重作用。
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Spectroscopic Assessment of Doxorubicin (DOX)-Gemcitabine (GEM) Gold Complex Nanovector as Diagnostic Tool of Galectin-1 Biomarker
Introduction The aim of this study is focused on the development of theranostic hybrid nanovectors based on gold-doxorubicin (DOX)-gemcitabine (GEM) complexes and their active targeting with Galectin-1 (Gal-1) as a promising therapeutic and prognostic marker in cancer. Methods For this purpose, a gold salt (HAuCl4) interacts with antitumor drugs (DOX; GEM) by chelation and then stabilizes with dicarboxylic acid-terminated polyethylene glycol (PEG) as a biocompatible surfactant. The proposed methodology is fast and reproducible, and leads to the formation of a hybrid nanovector named GEM@DOX IN PEG-AuNPs, in which the chemo-biological stability was improved. All synthetic chemical products were evaluated using various spectroscopic techniques (Raman and UV–Vis spectroscopy) and transmission electron microscopy (TEM). Results To conceive a therapeutic application, our hybrid nanovector (GEM@DOX IN PEG-AuNPs) was conjugated with the Galectin-1 protein (Gal-1) at different concentrations to predict and specifically recognize cancer cells. Gal-1 interacts with GEM@DOX in PEG-AuNPs, as shown by SPR and Raman measurements. We observed both dynamic variation in the plasmon position (SPR) and Raman band with Gal-1 concentration. Discussion We identified that GEM grafted electrostatically onto DOX IN PEG-AuNPs assumes a better chemical conformation, in which the amino group (NH3+) reacts with the carboxylic (COO−) group of PEG diacide, whereas the ciclopenthanol group at position C-5’ reacts with NH3+ of DOX. Conclusion This study opens further way in order to built “smart nanomedical devices” that could have a dual application as therapeutic and diagnostic in the field of nanomedicine and preclinical studies associated.
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