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.

抽象的我们中有10％以上的成年人患有各种肾脏疾病，这通常始于肾小球滤过屏障的微不足道损害，但很难在早期阶段检测到常规阶段生物标志物。但是，这种损害有时会导致严重的肾脏功能障碍而无需意识直到肾功能的60％以上。那是开发纳米医学，可以尽早发现肾小球功能障碍是肾脏疾病进展的最初一步，这是高度需要的，这是要求我们全面了解工程纳米颗粒（NP）的肾小球过滤。虽然已知肾小球滤过屏障“尺寸截止”缝隙，可保留工程的NP或蛋白质较大超过体内的6nm，并通过孩子们快速极端较小的人，我们最近发现肾脏一类Sub-NM谷胱甘肽涂层的金纳米颗粒（Sub-NM GS-Aunps）的清除显着在早期演变阶段被glomerulli放慢了速度，尽管他们终于清除了通过尿液系统的身体。令人惊讶的观察不仅提出了一个基本问题 Sub-NM工程NP与体内的肾小球屏障相互作用，但也有可能打开新的早期发现肾脏疾病的途径。该提议的目的是从根本上了解亚肾小球的肾小球滤过 NM Aunps并探索在早期检测中应用新发现的纳米生物相互作用的可行性肾小球损伤。提出了三个具体目标来实现目标：目标是调查具有明确尺寸和表面化学的亚NM AUNP的肾小球过滤。 AIM II是调查亚NM AuNP的肾小球滤过具有良好控制的肾小球内皮糖囊泡（GENG）降解。 AIM III是将NIR发射子NM AUNP应用于临床前的GENG损伤的早期检测设置。该应用程序的成功不仅会显着提高我们对工程NP的肾小球滤过，但也导致了一类新的肾脏纳米探针，以备早期检测 GENG损伤以高灵敏度，但在临床前环境中成本较低。而且，它也将放下肾脏纳米药物的未来翻译基础，用于早期诊断肾脏疾病。

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