Ultrabright Plasmonic-Fluor Nanosensor-Enabled Noninvasive Management of Pediatric Nephrotic Syndrome

超亮等离子体荧光纳米传感器支持小儿肾病综合征的无创治疗

• 批准号: 10593497
• 负责人: Ying Maggie Chen
• 金额: $ 23.58万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-06 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593497
• 关键词: Accounting; Acute; Acute Renal Failure with Renal Papillary Necrosis; Adopted; Affect; Albumins; Angiotensin-Converting Enzyme Inhibitors; Antibodies; Binding; Biological Assay; Blood; Blood Urea Nitrogen; Blood Volume; Caring; Child; Childhood; Clinical; Clinical Management; Coupled; Creatinine; Data; Decentralization; Dermal; Detection; Development; Diagnostic; Disease; Diuretics; Early Diagnosis; End stage renal failure; Enzyme Inhibitor Drugs; Exhibits; Fluoroimmunoassay; Future; Goals; Healthcare Systems; Home; Human; Hypoalbuminemia; Immunoassay; Immunosuppressive Agents; In Situ; Infant; Inherited; Intercellular Fluid; Kidney; Kidney Diseases; Lead; Methods; Modeling; Monitor; Mus; Nephrology; Nephrotic Syndrome; Newborn Infant; Pain Free; Painless; Patients; Pharmaceutical Preparations; Phase; Population; Pre-Clinical Model; Proteins; Proteinuria; Public Health; Reading; Renal function; Reproducibility; Research; Sampling; Serum; Serum Albumin; Source; Steroid-resistant idiopathic nephrotic syndrome; Suction; Techniques; Technology; Testing; Therapeutic immunosuppression; Thromboembolism; Translations; Urine; Vacuum; Venipunctures; acute toxicity; afferent nerve; base; clinical application; clinical care; clinically significant; diagnostic platform; diagnostic tool; experience; follow-up; improved; infection risk; innovation; kidney dysfunction; minimally invasive; mouse model; nanolabel; nanosensors; neonate; nephrotoxicity; non-invasive monitor; novel; novel diagnostics; pediatric patients; personalized care; plasmonics; point of care; point-of-care diagnostics; small molecule; technology validation; translational study; treatment response

Pediatric nephrotic syndrome (NS), characterized by proteinuria, hypoalbuminemia and progressive loss of kidney function, is a debilitating childhood kidney disease. In addition, steroid-resistant NS, accounting for about 10% of end- stage kidney disease in the pediatric population, may require long-term use of immunosuppressants that can cause nephrotoxicity. The daunting difficulty in pediatric venipuncture, as well as the small volume limit of maximum blood draw allowed for a single draw and within 2 months, especially in neonates, infants and young children, has limited close monitoring of kidney function in the active phase of NS. Moreover, urine dipstick test, as a semi-quantitative and not- always-reliable assay, is a crude way of evaluating the treatment response. It is also unable to assess the kidney function that may be compromised by volume contraction, routine use of diuretics and angiotensin-converting enzyme inhibitors, and drug-induced renal toxicity acutely. Thus, development of an innovative, pain-free and volume extraction-free, and highly sensitive biodiagnostic platform is imperative to improve the clinical care for pediatric NS patients. Bioanalyte-rich dermal interstitial fluid (ISF) provides a novel opportunity to achieve painless and effective biodiagnostic technologies. However, the clinical utility of ISF is limited by the current technology. Our goal is to develop our newly invented ultrabright plasmonic-fluor (PF)-enabled microneedle (MN) technology (PF-MN) as an ultrasensitive and minimally-invasive diagnostic tool for rapid sampling and quantification of ISF blood urea nitrogen (BUN) and creatinine (Cr) in point-of-care settings and at home. To accomplish our research goals, we will utilize a highly reproducible hereditary NS mouse model. In this preclinical model, we aim to determine concentrations of BUN and Cr in the dermal ISF by using PF-enhanced competitive immunoassay performed on MN. Furthermore, we will correlate their concentrations derived from MN-sampled ISF, extracted ISF and serum. A successful completion of our pioneering proposal may lead to a paradigm-shift in the newborn and pediatric diagnostics. It will also pave the way for future translational study in pediatric NS patients.

小儿肾病综合征 (NS) 的特点是蛋白尿、低蛋白血症和肾功能进行性丧失，是一种使人衰弱的儿童肾脏疾病。此外，类固醇抵抗性 NS 约占儿科终末期肾病的 10%，可能需要长期使用可引起肾毒性的免疫抑制剂。小儿静脉穿刺的艰巨难度，以及单次抽血和 2 个月内最大抽血量限制较小，尤其是新生儿、婴幼儿，限制了 NS 活动期肾功能的密切监测。此外，尿液试纸测试作为一种半定量且并不总是可靠的测定方法，是评估治疗反应的粗略方法。它也无法评估可能因容量收缩、常规使用利尿剂和血管紧张素转换酶抑制剂以及药物引起的急性肾毒性而损害的肾功能。因此，开发一种创新、无痛、免抽取体积、高灵敏度的生物诊断平台对于改善儿科 NS 患者的临床护理势在必行。 富含生物分析物的真皮间质液（ISF）为实现无痛且有效的生物诊断技术提供了新的机会。然而，ISF的临床应用受到当前技术的限制。我们的目标是开发新发明的超亮等离子体荧光 (PF) 微针 (MN) 技术 (PF-MN)，作为一种超灵敏、微创诊断工具，用于快速采样和定量 ISF 血尿素氮 (BUN) 和在护理点和家中测量肌酐 (Cr)。为了实现我们的研究目标，我们将利用高度可重复的遗传性 NS 小鼠模型。在此临床前模型中，我们的目标是通过使用 MN 上进行的 PF 增强竞争性免疫测定来确定真皮 ISF 中 BUN 和 Cr 的浓度。此外，我们还将关联来自 MN 采样的 ISF、提取的 ISF 和血清的浓度。 我们的开创性提案的成功完成可能会导致新生儿和儿科诊断的范式转变。它还将为未来儿科 NS 患者的转化研究铺平道路。