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Proteomic investigation on bio-corona of Au, Ag and Fe nanoparticles for the discovery of triple negative breast cancer serum protein biomarkers.
Journal of Proteomics ( IF 3.3 ) Pub Date : 2019-11-12 , DOI: 10.1016/j.jprot.2019.103581
María Del Pilar Chantada-Vázquez 1 , Antonio Castro López 2 , María García Vence 3 , Sergio Vázquez-Estévez 4 , Benigno Acea-Nebril 5 , David G Calatayud 6 , Teresa Jardiel 6 , Susana B Bravo 3 , Cristina Núñez 1
Affiliation  

Nowadays, there are no targeted therapeutic modalities for triple negative breast cancer (TNBC). This disease is associated with poor prognosis and worst clinical outcome because of the aggressive nature of the tumor, delayed diagnosis, and non-specific symptoms in the early stages. Therefore, identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes remains an urgent clinical requirement. New user-friendly and cheap methods for biomarker identification are needed, and nanotechnology offers new opportunities. When dispersed in blood, nanoparticles (NPs) are covered by a protein shell termed "protein corona" (PC). While alterations in protein patterns are challeging to detect by conventional blood analyses, PC acts as a "nano-concentrator" of serum proteins with affinity for NPs' surface. So, the characterization of PC could allow the detection of otherwise undetectable changes in protein concentration at an early stage of the disease or after chemotherapy or surgery. To explore this research idea, serum samples from 8 triple negative breast cancer (TNBC) patients and 8 patients without malignancy were allowed to interact with gold nanoparticles (AuNPs: 10.02 ± 0.91 nm), silver nanoparticles (AgNPs: 9.73 ± 1.70 nm) and magnetic nanoparticles (MNPs: (9.30 ± 0.67 nm). Here, in order to identify biomarker candidates in serum of TNBC patients, these nanomaterials were combined with electrophoretic separation (SDS-PAGE) to performed qualitative and quantitative comparisons of the serum proteomes of TNBC patients (n = 8) and healthy controls (n = 8) by liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis. The results were validated through a sequential window acquisition of all theoretical mass spectra (SWATH) analysis, performed in total serum samples (patients and controls) using this approach as a multiple reaction monitoring (MRM) analysis. SIGNIFICANCE: It is well known that several proteins presented in human serum are important biomarkers for the diagnosis or prognosis of different diseases, as triple negative breast cancer (TNBC). Determining how nanomaterials as gold nanoparticles (AuNPs: 10.02 ± 0.91 nm), silver nanoparticles (AgNPs: 9.73 ± 1.70 nm) and magnetic nanoparticles (MNPs: (9.30 ± 0.67 nm) interact with human serum will assist not only in understanding their effects on the biological system (biocompability and toxicity), but also to obtain information for developing novel nanomaterials with high specificity and selectivity towards proteins with an important biological function (prognostic and diagnostic protein biomarkers).

中文翻译:

蛋白质组学研究金,银和铁纳米粒子的生物电晕,以发现三阴性乳腺癌血清蛋白生物标志物。

如今,尚无针对性的三阴性乳腺癌(TNBC)的靶向治疗方法。由于肿瘤的侵袭性,诊断延迟和早期的非特异性症状,该疾病与不良的预后和最差的临床结果相关。因此,鉴定用于筛选和治疗目的的新型特异性TNBC血清生物标志物仍然是迫切的临床需求。需要新的,用户友好的,廉价的生物标志物识别方法,纳米技术提供了新的机会。当分散在血液中时,纳米颗粒(NPs)被称为“蛋白质电晕”(PC)的蛋白质外壳覆盖。通过常规的血液分析很难检测到蛋白质模式的改变,而PC则是对NPs表面具有亲和力的血清蛋白质的“纳米浓缩剂”。因此,PC的表征可以在疾病的早期,化学疗法或手术后检测出蛋白质浓度中其他无法检测到的变化。为了探索这一研究思路,允许来自8位三阴性乳腺癌(TNBC)患者和8位无恶性肿瘤的患者血清样品与金纳米颗粒(AuNPs:10.02±0.91 nm),银纳米颗粒(AgNPs:9.73±1.70 nm)和磁性纳米颗粒(MNPs:(9.30±0.67 nm)。此处,为了鉴定TNBC患者血清中的生物标志物候选物,将这些纳米材料与电泳分离(SDS-PAGE)结合使用,对TNBC血清蛋白质组进行定性和定量比较液相色谱串联质谱法(LC-MS / MS)分析患者(n = 8)和健康对照(n = 8)。通过使用所有方法(多反应监测(MRM)分析)在所有血清样本(患者和对照)中进行的所有理论质谱(SWATH)分析的顺序窗口采集来验证结果。意义:众所周知,人类血清中存在的几种蛋白质是诊断或预后不同疾病的重要生物标志物,如三阴性乳腺癌(TNBC)。确定纳米材料(如金纳米颗粒(AuNPs:10.02±0.91 nm),银纳米颗粒(AgNPs:9.73±1.70 nm)和磁性纳米颗粒(MNPs:(9.30±0.67 nm))如何与人血清相互作用将不仅有助于理解它们对人血清的影响。生物系统(生物相容性和毒性),
更新日期:2019-11-13
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