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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.

摘要在美国，超过10%的成年人患有各种肾脏疾病，这些疾病通常始于肾小球滤过屏障的轻微损伤，但在其早期阶段难以用常规方法检测到。生物标志物。然而，这种损害最终可能导致严重的肾功能障碍，而没有意识到直到超过60%的肾功能丧失因此，开发纳米药物，允许早期检测肾小球功能障碍是肾脏疾病进展的一个非常开始的步骤，需要我们对工程纳米颗粒（NPs）的肾小球过滤的全面理解。虽然肾小球滤过屏障是已知的“大小截止”狭缝，以保留较大的工程化NP或蛋白质，我们最近发现，肾脏中的小分子可以通过肾脏快速排出，一类亚纳米谷胱甘肽包被的金纳米颗粒（亚纳米GS-AuNPs）的清除率显著高于在早期消除阶段，尽管肾小球最终清除了细胞，但它们的速度仍被肾小球减慢。身体通过泌尿系统。这一令人惊讶的观察不仅提出了一个根本问题，亚纳米工程纳米粒子与肾小球屏障在体内相互作用，但也可能开辟一个新的早期发现肾脏疾病的途径。本提案的目的是从根本上了解亚慢性肾小球滤过，纳米金纳米粒子，并探讨应用新发现的纳米生物相互作用在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：肾小球过滤的亚纳米金纳米粒子具有明确的大小和表面化学。目的二是调查具有良好控制的肾小球内皮糖萼（GEnG）的亚nm AuNP的肾小球过滤降解目的III是应用近红外发射的亚纳米金纳米颗粒在临床前早期检测GEnG损伤。设置.申请的成功不仅将大大推进我们对工程化纳米颗粒的肾小球过滤，而且还导致一类新的肾脏纳米探针用于早期检测在临床前环境中以高灵敏度但低成本检测GEnG损伤。此外，它还将制定一项为肾脏纳米药物在肾脏疾病早期诊断中的应用奠定了基础。

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