Detail publikace

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.

Originální název

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

Typ

článek v časopise ve Web of Science, Jimp

Jazyk

angličtina

Originální abstrakt

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.

Klíčová slova

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

Autoři

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

Vydáno

26. 7. 2022

ISSN

1936-0851

Periodikum

ACS Nano

Ročník

16

Číslo

7

Stát

Spojené státy americké

Strany od

10517

Strany do

10533

Strany počet

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"
}