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），其特征是蛋白尿，低藻症和肾功能的进行性丧失，是一种使儿童肾脏疾病令人衰弱。此外，耐药的NS占小儿种群中末期肾脏疾病的约10％，可能需要长期使用可能引起肾毒性的免疫抑制剂。小儿静脉穿刺的艰巨难度，以及一次抽签的最大抽血的少量限制，在2个月内，尤其是在新生儿，婴儿和幼儿中，在NS的主动阶段对肾脏功能的密切监测有限。此外，作为一种半定量性且不始终可靠的测定，尿液量测试是评估治疗反应的粗略方法。它还无法评估可能因体积收缩，利尿剂和血管紧张素转化酶抑制剂的常规使用以及药物诱导的肾毒性而造成的肾功能。因此，必须开发创新，无痛和无体积提取以及高度敏感的生物诊断平台，这对于改善儿科NS患者的临床护理至关重要。 富含生物分析物的皮肤间质性液体（ISF）为获得无痛和有效的生物诊断技术提供了新的机会。但是，ISF的临床实用性受当前技术的限制。我们的目标是开发我们新发明的超级血浆 - 氟（PF）基于微酮（MN）技术（PF-MN）作为一种超敏感和微创的诊断工具，用于快速采样和量化ISF血液尿素氮（BUN）和肌酐（CR）和肌酐（CR）和肌酐（cr）。为了实现我们的研究目标，我们将利用高度重现的遗传NS鼠标模型。在此临床前模型中，我们旨在通过使用MN上执行的PF增强竞争性免疫测定法确定真皮ISF中的BUN和CR的浓度。此外，我们将将其浓度从Mn-Smplamped ISF，提取的ISF和血清相关联。 成功完成我们的开拓性建议可能会导致新生儿和儿科诊断的范式迁移。它还将为小儿NS患者的未来翻译研究铺平道路。