Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy

Sijia Yi, Xiaohan Zhang, M. Hussain Sangji, Yugang Liu, Sean D. Allen, Baixue Xiao, Sharan Bobbala, Cameron L. Braverman, Lei Cai, Peter I. Hecker, Matthew DeBerge, Edward Benjamin Thorp, Ryan E. Temel, Samuel Stupp, Evan Alexander Scott*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T-cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti-inflammatory agent 1,25-dihydroxyvitamin D3-(aVD) and ApoB-100-derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P-D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly low-dose intravenous administration of DC-targeted, aVD-loaded polymersomes significantly inhibit atherosclerotic lesion development in high-fat-diet-fed ApoE−/− mice. The results validate the key role of DC immunomodulation during aVD-dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell-targeted nanotherapy in the treatment of CVD.

Original languageEnglish (US)
Article number1904399
JournalAdvanced Functional Materials
Volume29
Issue number42
DOIs
StatePublished - Oct 1 2019

Fingerprint

Modulation
modulation
cells
lesions
arteriosclerosis
Peptides
peptides
chronic conditions
Apolipoprotein B-100
T-cells
Calcitriol
diets
dosage
Apolipoproteins E
Nutrition
Dendritic Cells
Oils and fats
Surface chemistry
regulators
fats

Keywords

  • atherosclerosis
  • dendritic cells
  • immunotherapy
  • polymersomes
  • targeted delivery

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

Cite this

Yi, Sijia ; Zhang, Xiaohan ; Sangji, M. Hussain ; Liu, Yugang ; Allen, Sean D. ; Xiao, Baixue ; Bobbala, Sharan ; Braverman, Cameron L. ; Cai, Lei ; Hecker, Peter I. ; DeBerge, Matthew ; Thorp, Edward Benjamin ; Temel, Ryan E. ; Stupp, Samuel ; Scott, Evan Alexander. / Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy. In: Advanced Functional Materials. 2019 ; Vol. 29, No. 42.
@article{9b9a0d264b3a4636b119ffcb7449dec3,
title = "Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy",
abstract = "The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T-cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti-inflammatory agent 1,25-dihydroxyvitamin D3-(aVD) and ApoB-100-derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P-D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly low-dose intravenous administration of DC-targeted, aVD-loaded polymersomes significantly inhibit atherosclerotic lesion development in high-fat-diet-fed ApoE−/− mice. The results validate the key role of DC immunomodulation during aVD-dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell-targeted nanotherapy in the treatment of CVD.",
keywords = "atherosclerosis, dendritic cells, immunotherapy, polymersomes, targeted delivery",
author = "Sijia Yi and Xiaohan Zhang and Sangji, {M. Hussain} and Yugang Liu and Allen, {Sean D.} and Baixue Xiao and Sharan Bobbala and Braverman, {Cameron L.} and Lei Cai and Hecker, {Peter I.} and Matthew DeBerge and Thorp, {Edward Benjamin} and Temel, {Ryan E.} and Samuel Stupp and Scott, {Evan Alexander}",
year = "2019",
month = "10",
day = "1",
doi = "10.1002/adfm.201904399",
language = "English (US)",
volume = "29",
journal = "Advanced Functional Materials",
issn = "1616-301X",
publisher = "Wiley-VCH Verlag",
number = "42",

}

Yi, S, Zhang, X, Sangji, MH, Liu, Y, Allen, SD, Xiao, B, Bobbala, S, Braverman, CL, Cai, L, Hecker, PI, DeBerge, M, Thorp, EB, Temel, RE, Stupp, S & Scott, EA 2019, 'Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy', Advanced Functional Materials, vol. 29, no. 42, 1904399. https://doi.org/10.1002/adfm.201904399

Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy. / Yi, Sijia; Zhang, Xiaohan; Sangji, M. Hussain; Liu, Yugang; Allen, Sean D.; Xiao, Baixue; Bobbala, Sharan; Braverman, Cameron L.; Cai, Lei; Hecker, Peter I.; DeBerge, Matthew; Thorp, Edward Benjamin; Temel, Ryan E.; Stupp, Samuel; Scott, Evan Alexander.

In: Advanced Functional Materials, Vol. 29, No. 42, 1904399, 01.10.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy

AU - Yi, Sijia

AU - Zhang, Xiaohan

AU - Sangji, M. Hussain

AU - Liu, Yugang

AU - Allen, Sean D.

AU - Xiao, Baixue

AU - Bobbala, Sharan

AU - Braverman, Cameron L.

AU - Cai, Lei

AU - Hecker, Peter I.

AU - DeBerge, Matthew

AU - Thorp, Edward Benjamin

AU - Temel, Ryan E.

AU - Stupp, Samuel

AU - Scott, Evan Alexander

PY - 2019/10/1

Y1 - 2019/10/1

N2 - The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T-cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti-inflammatory agent 1,25-dihydroxyvitamin D3-(aVD) and ApoB-100-derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P-D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly low-dose intravenous administration of DC-targeted, aVD-loaded polymersomes significantly inhibit atherosclerotic lesion development in high-fat-diet-fed ApoE−/− mice. The results validate the key role of DC immunomodulation during aVD-dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell-targeted nanotherapy in the treatment of CVD.

AB - The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T-cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti-inflammatory agent 1,25-dihydroxyvitamin D3-(aVD) and ApoB-100-derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P-D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly low-dose intravenous administration of DC-targeted, aVD-loaded polymersomes significantly inhibit atherosclerotic lesion development in high-fat-diet-fed ApoE−/− mice. The results validate the key role of DC immunomodulation during aVD-dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell-targeted nanotherapy in the treatment of CVD.

KW - atherosclerosis

KW - dendritic cells

KW - immunotherapy

KW - polymersomes

KW - targeted delivery

UR - http://www.scopus.com/inward/record.url?scp=85070715953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070715953&partnerID=8YFLogxK

U2 - 10.1002/adfm.201904399

DO - 10.1002/adfm.201904399

M3 - Article

AN - SCOPUS:85070715953

VL - 29

JO - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-301X

IS - 42

M1 - 1904399

ER -