Zhou Jing's group and collaborators constructed blood flow shear-responsive nanodiscs that can be used to resist vascular endothelial inflammation and atherosclerosis

On November 20, 2022, the research group of Zhou Jing, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, and Gan Yong, Yu Miaorong, and others from the Shanghai Institute of Materia Medica, Peking University Health Science Center, published an online report in Small magazine Disturbed flow-facilitated margination and targeting of nanodisks protect against atherosclerosis
.
Compared with spherical nanoparticles, disc-shaped nanoparticles were enriched in the turbulent region of the shear loading model of blood flow in the body, interior and exterior.
Nanodisc loading of DNA methyltransferase inhibitor decitabine can exert local anti-inflammatory and anti-atherosclerotic effects, and reduce the toxic side effects of drugs, indicating that discoid nanoparticles can be used as a better systematic treatment for
cardiovascular therapy targeted drug delivery.

Figure: Blood flow shear responsive nanodiscs for anti-vascular endothelial inflammation and atherosclerosis

Atherosclerosis is a systemic disease involving multiple vessels that occurs in specific areas of the arterial tree: bifurcations and bends of arteries
.
Blood flow in these areas produces low, irregularly oriented shear forces that promote atherosclerosis by inducing vascular inflammation and endothelial dysfunction such as endothelial cell hyperproliferation and apoptosis
.
Reducing endothelial cell inflammation caused by turbulence has become a key entry point
for the development of endothelial protection and anti-atherosclerotic strategies.
Nano-drug delivery systems can improve the effect of local treatment and reduce the toxicity
of off-target organs in the treatment of atherosclerosis.
By optimizing their shape, size and surface chemistry, they can be delivered
to specific parts.

In this study, disc-shaped and spherical mesoporous silica nanoparticles (MSND vs.
MSNS) were prepared for use in vitro using "vertical step fluids.
" Models (simultaneous observation of deposition of nanoparticles of different shapes in turbulent and laminar flow states at the same level), vascular stenosis microfluidic models (real-time observation of deposition of nanoparticles of different shapes in turbulent regions), naturally developed laminar flow zones (descending thoracic aorta) and turbulent regions (aortic arch) in mice, and C57/BL6 Mice undergo partial carotid artery ligation to construct in vivo turbulence models (real-time observation of the deposition of differently-shaped nanoparticles in blood vessels in the turbulent region) to evaluate the effect
of shape on targeted delivery of drug-loaded nanoparticles to the vascular turbulence region.
The results showed that MSND preferentially accumulated in the vascular endothelium in the turbulent region of pro-atherosclerosis, and determined the therapeutic effects
of shape optimization and drug-loaded nanoparticles in preventing endothelial inflammation.
This study provides a mechanobiological basis for optimizing the systematic regimen of cardiovascular targeted therapy, and provides some guidance
for the rational design of drug-loaded nanoparticles in atherosclerotic therapy in the future.

Professor Jing Zhou of the School of Basic Medicine of Peking University and Professor Gan Yong and Miaorong Yu of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences are co-corresponding authors
of this research paper.
Zhao Chuanrong, a postdoctoral fellow at Peking University School of Basic Medical Sciences, Li Jingyi, a graduate student at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Jiang Zhitong, a Ph.
D.
in human physiology from Peking University School of Basic Medical Sciences, are co-first authors
of this paper.
This research was supported
by the National Natural Science Foundation of China's Major Research Program Integration Project, Innovative Research Group and General Project.
Zhou Jing's research group has long been engaged in the study of vascular homeostasis and the mechanical regulation mechanism of diseases, and the results were published in Proc.
Nat.
Acad.
Sci.
USA, Biomaterials, Circ Res and other academic journals
.

Article link: https://doi.
org/10.
1002/smll.
202204694

(School of Basic Medicine, Peking University)