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用于靶向缺血性中风干预的心房利钠肽抗体功能化聚乙二醇化多壁碳纳米管

Atrial Natriuretic Peptide Antibody-Functionalised, PEGylated Multiwalled Carbon Nanotubes for Targeted Ischemic Stroke Intervention.

作者信息

Komane Patrick P, Kumar Pradeep, Choonara Yahya E

机构信息

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Johannesburg 2193, South Africa.

Department of Chemical Sciences, University of Johannesburg, 27 Nind Street, Johannesburg 2028, South Africa.

出版信息

Pharmaceutics. 2021 Aug 28;13(9):1357. doi: 10.3390/pharmaceutics13091357.

DOI:10.3390/pharmaceutics13091357
PMID:34575433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8471373/
Abstract

Stroke is one of the major causes of disability and the second major cause of death around the globe. There is a dire need for an ultrasensitive detection tool and an effective and efficient therapeutic system for both detection and treatment of stroke at its infancy stage. Carbon nanotubes are promising nanomaterials for tackling these challenges. The loading of dexamethasone and decoration of PEGylated multiwalled carbon nanotube with atrial natriuretic peptide (ANP) antibody and fluorescein isothiocyanate for targeting ischemic site in the rat stroke model is presented here. Functionalisation of carbon nanotubes with dexamethasone (DEX), polyethylene glycol (PEG), fluorescein isothiocyanate (FITC), and ANP antibody caused a 63-fold increase in the D band intensity as illustrated by Raman. The characteristic band intensity increase was observed at 1636 nm following functionalisation of carbon nanotubes with polyethylene glycol and dexamethasone as confirmed by Fourier Transform Infrared. These findings have demonstrated the coupling capability of atrial natriuretic peptide antibody to DEX-PEG-CNTs. The baseline plasma atrial natriuretic peptide levels were ranging from 118 to 135.70 pg/mL prior to surgery and from 522.09 to 552.37 following common carotid artery occlusion. A decrease in atrial natriuretic peptide levels to 307.77 was observed when the rats were treated with FITC-DEX-PEG-ANP-CNTs, PEG-CNTs and DEX with a significant drop in the FITC-DEX-PEG-ANP-CNTs treated group. Fluorescence was detected in FITC-DEX-PEG-CNTs and FITC-DEX-PEG-ANP-CNTs treated ischemic stroke rats. The highest fluorescence intensity was reported in plasma (2179) followed by the kidney (1563) and liver (1507). These findings suggest a beneficial role that is played by the FITC-DEX-PEG-ANP-CNTs in the reduction of inflammation in the ischemic stroke induced rats that could induce a successful treatment of ischemic stroke.

摘要

中风是全球致残的主要原因之一,也是第二大死因。迫切需要一种超灵敏的检测工具以及一种有效且高效的治疗系统,用于在中风的初期阶段进行检测和治疗。碳纳米管是应对这些挑战的有前景的纳米材料。本文介绍了在大鼠中风模型中,用去甲肾上腺素(ANP)抗体和异硫氰酸荧光素对聚乙二醇化多壁碳纳米管进行地塞米松负载和修饰,以靶向缺血部位。用拉曼光谱表明,用去甲肾上腺素(DEX)、聚乙二醇(PEG)、异硫氰酸荧光素(FITC)和ANP抗体对碳纳米管进行功能化处理后,D带强度增加了63倍。傅里叶变换红外光谱证实,在用聚乙二醇和地塞米松对碳纳米管进行功能化处理后,在1636nm处观察到特征带强度增加。这些发现证明了心房钠尿肽抗体与DEX-PEG-CNTs的偶联能力。手术前血浆心房钠尿肽水平基线为118至135.70pg/mL,颈总动脉闭塞后为522.09至552.37pg/mL。当用FITC-DEX-PEG-ANP-CNTs、PEG-CNTs和DEX治疗大鼠时,观察到心房钠尿肽水平降至307.77,在FITC-DEX-PEG-ANP-CNTs治疗组中有显著下降。在FITC-DEX-PEG-CNTs和FITC-DEX-PEG-ANP-CNTs治疗的缺血性中风大鼠中检测到荧光。血浆中荧光强度最高(2179),其次是肾脏(1563)和肝脏(1507)。这些发现表明,FITC-DEX-PEG-ANP-CNTs在减少缺血性中风诱导大鼠的炎症方面发挥了有益作用,这可能会成功治疗缺血性中风。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/7b14938c6223/pharmaceutics-13-01357-g013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/4cd2504a97e5/pharmaceutics-13-01357-sch001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/b4d9b89adfdc/pharmaceutics-13-01357-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/8483ae2cb65b/pharmaceutics-13-01357-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/cf81d586f2b1/pharmaceutics-13-01357-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/57de6a115bef/pharmaceutics-13-01357-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/487cfc35490f/pharmaceutics-13-01357-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/7b14938c6223/pharmaceutics-13-01357-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/3ea6bb4c5956/pharmaceutics-13-01357-ch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/df53a0dd18fd/pharmaceutics-13-01357-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/89995e8663c5/pharmaceutics-13-01357-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/4cd2504a97e5/pharmaceutics-13-01357-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/095e0953fd1f/pharmaceutics-13-01357-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/3a56055ec9c3/pharmaceutics-13-01357-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/9cbe537d2b1f/pharmaceutics-13-01357-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/5153fc6aa825/pharmaceutics-13-01357-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/d511d8ffeb43/pharmaceutics-13-01357-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/b4d9b89adfdc/pharmaceutics-13-01357-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/8483ae2cb65b/pharmaceutics-13-01357-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/cf81d586f2b1/pharmaceutics-13-01357-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/57de6a115bef/pharmaceutics-13-01357-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/487cfc35490f/pharmaceutics-13-01357-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6958/8471373/7b14938c6223/pharmaceutics-13-01357-g013.jpg

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