A DNA Nanoraft-Based Cytokine Delivery Platform for Alleviation of Acute Kidney Injury.
Wei LiChengshi WangHui LvZhenghao WangMeng ZhaoShuyun LiuLiping GouYe ZhouJuan LiJiayi ZhangLan LiYizhuo WangPeng LouLei WuLi ZhouYounan ChenYanrong LuJingqiu ChengYuan-Ping HanQi CaoWei HuangNanwei TongXianghui FuJingping LiuXiaofeng ZhengPer-Olof BerggrenPublished in: ACS nano (2021)
Cytokine immunotherapy represents an attractive strategy to stimulate robust immune responses for renal injury repair in ischemic acute kidney injury (AKI). However, its clinical application is hindered by its nonspecificity to kidney, short circulation half-life, and severe side effects. An ideal cytokine immunotherapy for AKI requires preferential delivery of cytokines with accurate dosage to the kidney and sustained-release of cytokines to stimulate the immune responses. Herein, we developed a DNA nanoraft cytokine by precisely arranging interleukin-33 (IL-33) nanoarray on rectangle DNA origami, through which IL-33 can be preferentially delivered to the kidney for alleviation of AKI. A nanoraft carrying precisely quantified IL-33 predominantly accumulated in the kidney for up to 48 h. Long-term sustained-release of IL-33 from nanoraft induced rapid expansion of type 2 innate lymphoid cells (ILC 2s) and regulatory T cells (Tregs) and achieved better treatment efficiency compared to free IL-33 treatment. Thus, our study demonstrates that a nanoraft can serve as a structurally well-defined delivery platform for cytokine immunotherapy in ischemic AKI and other renal diseases.
Keyphrases
- acute kidney injury
- cardiac surgery
- immune response
- regulatory t cells
- dendritic cells
- induced apoptosis
- high throughput
- single molecule
- toll like receptor
- ischemia reperfusion injury
- high resolution
- mass spectrometry
- cell proliferation
- diabetic rats
- replacement therapy
- single cell
- endoplasmic reticulum stress
- subarachnoid hemorrhage