Sequential Therapy of Acute Kidney Injury with a DNA Nanodevice

被引：72

作者：

Chen, Qian ^{[1
]}

Ding, Fei ^{[2
]}

Zhang, Shuangye ^{[2
]}

Li, Qian ^{[2
]}

Liu, Xiaoguo ^{[2
]}

Song, Haiyun ^{[3
]}

Zuo, Xiaolei ^{[4
,5
]}

Fan, Chunhai ^{[2
]}

Mou, Shan ^{[1
]}

Ge, Zhilei ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Nephrol, Shanghai 200127, Peoples R China

[2] Shanghai Jiao Tong Univ, Natl Ctr Translat Med, Frontiers Sci Ctr Transformat Mol, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China

[3] Shanghai Jiao Tong Univ, Ctr Single Cell Omics, Sch Publ Hlth, State Key Lab Oncogenes & Related Genes,Sch Med, Shanghai 200025, Peoples R China

[4] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Inst Mol Med,Shanghai Key Lab Nucle Acid Chem & N, Shanghai 200127, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Chem & Chem Engn, Shanghai 200127, Peoples R China

来源：

NANO LETTERS | 2021年 / 21卷 / 10期

基金：

上海市自然科学基金; 中国国家自然科学基金; 国家重点研发计划;

关键词：

DNA nanotechnology; nanodevice; framework nucleic acids; renal ischemia-reperfusion injury; sequential therapy; PREFERENTIAL RENAL UPTAKE; OXIDATIVE STRESS; C5A; NANOPARTICLES; COMPLEMENT; NANOSTRUCTURES;

D O I：

10.1021/acs.nanolett.1c01044

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The high demand for acute kidney injury (AKI) therapy calls the development of multifunctional nanomedicine for renal management with programmable pharmacokinetics. Here, we developed a renal-accumulating DNA nanodevice with exclusive kidney retention for longitudinal protection of AKI in different stages in a renal ischemia-reperfusion (I/R) model. Due to the prolonged kidney retention time (>12 h), the ROS-sensitive nucleic acids of the nanodevice could effectively alleviate oxidative stress by scavenging ROS in stage I, and then the anticomplement component 5a (aC5a) aptamer loaded nanodevice could sequentially suppress the inflammatory responses by blocking C5a in stage II, which is directly related to the cytokine storm. This sequential therapy provides durable and pathogenic treatment of kidney dysfunction based on successive pathophysiological events induced by I/R, which holds great promise for renal management and the suppression of the cytokine storm in more broad settings including COVID-19.

引用

页码：4394 / 4402

页数：9

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