Bevilacqua Giulio, Corvino Roberta, Capriotti Anna Laura, Montone Carmela Maria, Moriconi Martina, Salciccia Stefano, Brunelli Valentina, Santarelli Valerio, Sciarra Beatrice, Laganà Aldo, Santini Daniele, Sciarra Alessandro, Gentilucci Alessandro
Department "Materno Infantile e Scienze Urologiche", University Sapienza, 00161 Rome, Italy.
Department of Chemistry, University Sapienza, 00161 Rome, Italy.
Biology (Basel). 2024 Dec 7;13(12):1024. doi: 10.3390/biology13121024.
The National Cancer Institute (NCI) recognizes the potential of technologies based on the use of nanoparticles (NPs) in revolutionizing clinical approaches to the diagnosis and prognosis of cancer. Recent research suggests that once NPs come into contact with the biological fluid of cancer patients, they are covered by proteins, forming a "protein corona" composed of hundreds of plasma proteins. The concept of a personalized, disease-specific protein corona, demonstrating substantial differences in NP corona profiles between patients with and without cancer, has been introduced. We developed the design of an experimental prospective single-center study with patients allocated in a 1:1:1 ratio of one of three arms: untreated patients with benign prostatic hyperplasia (BPH), untreated patients with non-metastatic prostate cancer (PCa), and metastatic prostate cancer patients starting systemic therapies with new androgen-targeted agents or taxanes. The protocol aims to develop and implement sensitive nanotools with two distinct objectives: First, to design NPs capable of selectively binding and detecting biomarkers in order to build a predictive diagnostic model to effectively discriminate between patient sera affected by BPH and PCa. Secondly, within the population with PCa, in the case of initial advanced metastatic diagnosis, the objective is to find biomarkers capable of predicting the response to systemic treatments to improve the precision and efficiency of monitoring treatment outcomes. For protein and metabolite corona experiments, we developed a cross-reactive sensor array platform with cancer detection capacity made of three liposomal formulations with different surface charges. For proteomic-NP studies, proteins were identified and quantified using nano-high-performance LC (nanoHPLC) coupled with MS/MS (nanoHPLC-MS/MS). Metabolites were instead analyzed using an untargeted metabolomic approach. Compared with previous review articles, the novelty of this review is represented by the analysis of the possible clinical applications of protein corona NPs focused on PCa and the presentation of a new clinical protocol in the metastatic phase of PCa.
美国国立癌症研究所（NCI）认识到基于纳米颗粒（NP）的技术在彻底改变癌症诊断和预后的临床方法方面的潜力。最近的研究表明，一旦NP与癌症患者的生物体液接触，它们就会被蛋白质覆盖，形成由数百种血浆蛋白组成的“蛋白质冠”。个性化、疾病特异性蛋白质冠的概念已经被引入，它表明癌症患者和非癌症患者的NP冠谱存在显著差异。我们开展了一项实验性前瞻性单中心研究的设计，将患者按1:1:1的比例分配到三个组中的一组：未经治疗的良性前列腺增生（BPH）患者、未经治疗的非转移性前列腺癌（PCa）患者，以及开始使用新型雄激素靶向药物或紫杉烷进行全身治疗的转移性前列腺癌患者。该方案旨在开发和实施具有两个不同目标的灵敏纳米工具：第一，设计能够选择性结合和检测生物标志物的NP，以建立一个预测诊断模型，有效区分受BPH和PCa影响的患者血清。其次，在PCa患者群体中，对于初始晚期转移性诊断的情况，目标是找到能够预测对全身治疗反应的生物标志物，以提高监测治疗结果的精度和效率。对于蛋白质和代谢物冠实验，我们开发了一种具有癌症检测能力的交叉反应传感器阵列平台，该平台由三种具有不同表面电荷的脂质体制剂制成。对于蛋白质组学-NP研究，使用纳升级高效液相色谱（nanoHPLC）与串联质谱（nanoHPLC-MS/MS）联用对蛋白质进行鉴定和定量。代谢物则采用非靶向代谢组学方法进行分析。与之前的综述文章相比，本综述的新颖之处在于分析了聚焦于PCa的蛋白质冠NP的可能临床应用，并展示了PCa转移期的一项新临床方案。
