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Glomerular Filtration of Sub-nm Gold Nanoparticles

亚纳米金纳米颗粒的肾小球滤过

基本信息

批准号：
10188515
负责人：
Jie Zheng
金额：
$ 35.58万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10188515
关键词：
Address Adult Affinity Artificial nanoparticles Awareness Basement membrane Biological Markers Caliber Charge Chemical Engineering Chemistry Data Dependence Development Dextrans Diagnostic radiologic examination Disease Progression Dyes Early Diagnosis Electrons Endothelium Filtration Foundations Functional disorder Future Glomerular Capillary Glutathione Glycocalyx Image Injury Kidney Kidney Diseases Kinetics Lead Medical Microscopic Mind Modeling Molecular Nanotechnology Nature Non-Invasive Cancer Detection Pathway interactions Physiology Proteins Radial Renal clearance function Renal function Series Surface System Textbooks Time Translations Urinary system clinical translation cost design drug testing fluorescence imaging glomerular endothelium glomerular filtration in vivo kidney dysfunction kidney imaging nano nanoGold nanomedicine nanoparticle nanoprobe news podocyte pre-clinical success tool

项目摘要

Abstract More than 10% of adults in US are suffering from a variety of kidney diseases, which often start with trivial damages to the glomerular filtration barrier but are hard to detect in their early stages with conventional biomarkers. However, such damages can eventually lead to severe kidney dysfunctions without awareness until more than 60% of kidney function is lost. Thus, developing nanomedicines that allow early detection of glomerular dysfunction, a very beginning step in the kidney disease progression, is highly desired, which demands our comprehensive understanding of the glomerular filtration of engineered nanoparticles (NPs). While the glomerular filtration barrier is known a “size cut-off” slit to retain engineered NPs or proteins larger than 6nm in the body and to rapidly excrete the smaller ones through the kidneys, we recently found that renal clearance of a class of sub-nm glutathione coated gold nanoparticles (sub-nm GS-AuNPs) was significantly slowed down by the glomeruli in the early elimination stage even though they eventually cleared out of the body through the urinary system. This surprising observation not only raises a fundamental question of how sub-nm engineered NPs interact with the glomerular barrier in vivo but potentially also opens up a new pathway for early detection of kidney diseases. The objective of this proposal is to fundamentally understand the glomerular filtration of sub- nm AuNPs and explore the feasibility of applying the newly discovered nano-bio interactions in early detection of glomerular injury. Three specific aims are proposed to accomplish the objective: Aim I is to investigate glomerular filtration of sub-nm AuNPs with well-defined size and surface chemistries. Aim II is to investigate glomerular filtration of sub-nm AuNPs with well-controlled glomerular endothelial glycocalyx (GEnG) degradation. Aim III is to apply NIR-emitting sub-nm AuNPs for early detection of GEnG injury in the preclinical settings. The success of the application will not only significantly advance our fundamental understanding of the glomerular filtration of engineered NPs but also lead to a new class of renal nanoprobes for early detection of GEnG injury at high sensitivity but low cost in the preclinical settings. Moreover, it will also lay down a foundation for future translation of renal nanomedicines for early diagnosis of kidney diseases.

抽象的美国超过 10% 的成年人患有各种肾脏疾病，这些疾病通常始于对肾小球滤过屏障造成轻微损害，但在早期阶段很难用传统方法检测到生物标志物。然而，这种损害最终可能在不知不觉中导致严重的肾功能障碍直至肾功能丧失60%以上。因此，开发能够早期检测的纳米药物肾小球功能障碍是肾脏疾病进展的第一步，是非常需要的，这需要我们全面了解工程纳米粒子（NP）的肾小球滤过。虽然肾小球滤过屏障被称为“尺寸截止”狭缝，以保留较大的工程纳米粒子或蛋白质体内小于6nm的物质，并通过肾脏快速排出较小的物质，我们最近发现肾一类亚纳米谷胱甘肽包被的金纳米颗粒（亚纳米 GS-AuNPs）的清除率显着提高尽管肾小球最终清除了肾小球，但它们在早期消除阶段减慢了速度身体通过泌尿系统。这一令人惊讶的观察不仅提出了一个基本问题：亚纳米工程纳米粒子在体内与肾小球屏障相互作用，但也可能开辟新的途径早期发现肾脏疾病的途径。该提案的目的是从根本上了解亚细胞的肾小球滤过纳米金纳米粒子并探索将新发现的纳米生物相互作用应用于早期检测的可行性肾小球损伤。为实现这一目标，提出了三个具体目标：目标 I 是进行调查具有明确尺寸和表面化学性质的亚纳米金纳米粒子的肾小球滤过。目标二是调查具有良好控制的肾小球内皮糖萼 (GEnG) 的亚纳米 AuNP 的肾小球滤过降解。目标 III 是应用近红外发射亚纳米 AuNP 在临床前早期检测 GEnG 损伤设置。该应用的成功不仅将显着增进我们对工程化纳米颗粒的肾小球滤过，同时也催生了一类用于早期检测的新型肾脏纳米探针在临床前环境中以高灵敏度但低成本检测 GEnG 损伤。此外，还将制定为未来将肾脏纳米药物转化为肾脏疾病的早期诊断奠定了基础。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Proximal tubules eliminate endocytosed gold nanoparticles through an organelle-extrusion-mediated self-renewal mechanism

DOI：
10.1038/s41565-023-01366-7
发表时间：
2023-04-17
期刊：
NATURE NANOTECHNOLOGY
影响因子：
38.3
作者：
Huang, Yingyu;Yu, Mengxiao;Zheng, Jie
通讯作者：
Zheng, Jie

Renal Clearable Luminescent Gold Nanoparticles: From the Bench to the Clinic.

DOI：
10.1002/anie.201807847
发表时间：
2019-03-22
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
0
作者：
Yu M;Xu J;Zheng J
通讯作者：
Zheng J

In Situ Ligand-Directed Growth of Gold Nanoparticles in Biological Tissues.

DOI：
10.1021/acs.nanolett.9b04911
发表时间：
2020-02-12
期刊：
Nano letters
影响因子：
10.8
作者：
Peng C;Yu M;Zheng J
通讯作者：
Zheng J

Noninvasive monitoring of hepatic glutathione depletion through fluorescence imaging and blood testing.

DOI：
10.1126/sciadv.abd9847
发表时间：
2021-03
期刊：
Science advances
影响因子：
13.6
作者：
Jiang X;Zhou Q;Du B;Li S;Huang Y;Chi Z;Lee WM;Yu M;Zheng J
通讯作者：
Zheng J

Renal clearable nanocarriers: Overcoming the physiological barriers for precise drug delivery and clearance.

DOI：
10.1016/j.jconrel.2020.03.020
发表时间：
2020-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
0
作者：
Peng C;Huang Y;Zheng J
通讯作者：
Zheng J