Proteomic investigation on bio-corona of Au, Ag and Fe nanoparticles for the discovery of triple negative breast cancer serum protein biomarkers
Proteomic investigation on bio-corona of Au, Ag and Fe nanoparticles for the discovery of triple negative breast cancer serum protein biomarkers
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DOI：
10.1016/j.jprot.2019.103581
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发表时间：
2020-02-10
影响因子：
3.3
通讯作者：
Nunez, Cristina
中科院分区：
文献类型：
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作者：
del Pilar Chantada-Vazquez, Maria;Castro Lopez, Antonio;Nunez, Cristina
目前，还没有针对三阴性乳腺癌（TNBC）的靶向治疗方式。由于肿瘤的侵袭性、延迟诊断和早期非特异性症状，这种疾病与预后差和最差的临床结果相关。因此，鉴定用于筛查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。需要新的用户友好和廉价的生物标志物鉴定方法，纳米技术提供了新的机会。当分散在血液中时，纳米颗粒（NP）被称为“蛋白质冠”（PC）的蛋白质壳覆盖。虽然蛋白质模式的改变对通过常规血液分析检测具有挑战性，但PC充当血清蛋白的“纳米浓缩器”，对NP的表面具有亲和力。因此，PC的表征可以在疾病的早期阶段或化疗或手术后检测到蛋白质浓度的变化，为了探索这一研究思路，允许来自8名三阴性乳腺癌（TNBC）患者和8名非恶性肿瘤患者的血清样品与金纳米颗粒相互作用（AuNP：10.02 +/-0.91 nm）、银纳米颗粒（AgNP：9.73 +/-1.70 nm）和磁性纳米颗粒（MNP：（9.30 +/-0.67 nm）。在此，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）相结合，通过液相色谱串联质谱（LC-MS/MS）分析对TNBC患者（n = 8）和健康对照（n = 8）的血清蛋白质组进行定性和定量比较。结果通过连续窗口采集所有理论质谱（SWATH）分析进行验证，使用这种方法作为多反应监测（MRM）分析在总血清样品（患者和对照）中进行。意义：众所周知，人血清中存在的几种蛋白质是用于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（MNP：（9.30 +/- 0.67 nm）与人血清相互作用不仅有助于了解它们对生物系统的影响，（生物相容性和毒性），而且还获得用于开发对具有重要生物学功能（预后和诊断蛋白质生物标志物）的蛋白质具有高特异性和选择性的新型纳米材料的信息。
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 nano-materials 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).