Publication detail

Turning Hot into Cold: Immune Microenvironment Reshaping for Atherosclerosis Attenuation Based on pH-Responsive shSiglec-1 Delivery System

ZHOU, Y. WANG, SY. LIANG, XY. HEGER, Z. XU, M. LU, Q. YU, M. ADAM, V. LI, N.

Original Title

Turning Hot into Cold: Immune Microenvironment Reshaping for Atherosclerosis Attenuation Based on pH-Responsive shSiglec-1 Delivery System

Type

journal article in Web of Science

Language

English

Original Abstract

Current atherosclerosis treatment is based on a combination of cholesterol-lowering medication and low-fat diets; however, the clinical effect is unsatisfactory. It has been shown that the level of immune cell infiltration and pro-inflammatory factors in the atherosclerotic immune microenvironment (AIM) play important roles in the development and progression of atherosclerosis. Therefore, we hypothesized that reshaping "hot AIM" into "cold AIM" could attenuate atherosclerosis. For this purpose, we designed a pH-responsive and charge-reversible nanosystem, referred to as Au-PEI/ shSiglec-1/PEI-acetylsalicylic acid (ASPA NPs) to effectively deliver shSiglec1, which blocked the interactions between macrophages with CD8+ T/NKT cells, thus inhibiting immune cell infiltration. Further, we demonstrated that acetylsalicylic acid (ASA), detached from the pH-responsive PEI-ASA polymer, and inhibited lipid accumulation in macrophage, thereby decreasing the lipid antigen presentation. Additionally, reduced macrophage-produced inflammatory factors by ASA and low CD8+ T/NKT cell infiltration levels synergistically inhibit Th17 cell differentiation, thus further dramatically attenuating inflammation in AIM by decreasing the IL-17A production. Eventually, ASPA NPs efficiently reshaped AIM by inhibiting immune cell infiltration, lipid antigen presentation, and pro-inflammation, which provided a feasible therapeutic strategy for atherosclerosis immunotherapy.

Keywords

atherosclerosis; immune cell recruitment; antigen presentation; atherosclerotic immune microenvironment reshaping; shSiglec-1

Authors

ZHOU, Y.; WANG, SY.; LIANG, XY.; HEGER, Z.; XU, M.; LU, Q.; YU, M.; ADAM, V.; LI, N.

Released

26. 7. 2022

ISBN

1936-0851

Periodical

ACS Nano

Year of study

16

Number

7

State

United States of America

Pages from

10517

Pages to

10533

Pages count

17

URL

https://doi.org/10.1021/acsnano.2c01778

BibTex

@article{BUT179430,
  author="ZHOU, Y. and WANG, SY. and LIANG, XY. and HEGER, Z. and XU, M. and LU, Q. and YU, M. and ADAM, V. and LI, N.",
  title="Turning Hot into Cold: Immune Microenvironment Reshaping for Atherosclerosis Attenuation Based on pH-Responsive shSiglec-1 Delivery System",
  journal="ACS Nano",
  year="2022",
  volume="16",
  number="7",
  pages="10517--10533",
  doi="10.1021/acsnano.2c01778",
  issn="1936-0851",
  url="https://doi.org/10.1021/acsnano.2c01778"
}