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 B. Thorp; Ryan E. Temel; Samuel I. Stupp; Evan A. Scott

doi:10.1002/adfm.201904399

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 B. Thorp, Ryan E. Temel, Samuel I. Stupp, Evan A. Scott

Physiology

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

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 language	English
Article number	1904399
Journal	Advanced Functional Materials
Volume	29
Issue number	42
DOIs	https://doi.org/10.1002/adfm.201904399
State	Published - Oct 1 2019

Bibliographical note

Funding Information:
The authors would like to thank C. Reardon and G. Getz for advice, training, and protocols regarding the extraction and analysis of mouse aortas. The authors also thank J. Remis for CryoTEM assistance and the following facilities at Northwestern University: Robert H. Lurie Comprehensive Cancer Center Flow Cytometry Core; Center for Advanced Molecular Imaging; Biological imaging facility; Mouse Histology and Phenotyping Laboratory; Biological imaging facility and Keck-II facility of Northwestern University's NUANCE Center. This research was supported by the National Science Foundation CAREER Award (grant no. 1453576), the National Institutes of Health Director's New Innovator Award (grant no. 1DP2HL132390-01), American Heart Association (AHA) Postdoctoral Fellowship (17POST33670713), and the Louis A. Simpson & Kimberly K. Querrey Center for Regenerative Nanomedicine Regenerative Nanomedicine Catalyst Award.

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

atherosclerosis
dendritic cells
immunotherapy
polymersomes
targeted delivery

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/adfm.201904399

Cite this

Yi, S., Zhang, X., Sangji, M. H., Liu, Y., Allen, S. D., Xiao, B., Bobbala, S., Braverman, C. L., Cai, L., Hecker, P. I., DeBerge, M., Thorp, E. B., Temel, R. E., Stupp, S. I., & Scott, E. A. (2019). Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy. Advanced Functional Materials, 29(42), Article 1904399. https://doi.org/10.1002/adfm.201904399

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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 B.} and Temel, {Ryan E.} and Stupp, {Samuel I.} and Scott, {Evan A.}",

note = "Funding Information: The authors would like to thank C. Reardon and G. Getz for advice, training, and protocols regarding the extraction and analysis of mouse aortas. The authors also thank J. Remis for CryoTEM assistance and the following facilities at Northwestern University: Robert H. Lurie Comprehensive Cancer Center Flow Cytometry Core; Center for Advanced Molecular Imaging; Biological imaging facility; Mouse Histology and Phenotyping Laboratory; Biological imaging facility and Keck-II facility of Northwestern University's NUANCE Center. This research was supported by the National Science Foundation CAREER Award (grant no. 1453576), the National Institutes of Health Director's New Innovator Award (grant no. 1DP2HL132390-01), American Heart Association (AHA) Postdoctoral Fellowship (17POST33670713), and the Louis A. Simpson & Kimberly K. Querrey Center for Regenerative Nanomedicine Regenerative Nanomedicine Catalyst Award. Publisher Copyright: {\textcopyright} 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

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doi = "10.1002/adfm.201904399",

language = "English",

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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, SI & 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

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 B.

AU - Temel, Ryan E.

AU - Stupp, Samuel I.

AU - Scott, Evan A.

N1 - Funding Information: The authors would like to thank C. Reardon and G. Getz for advice, training, and protocols regarding the extraction and analysis of mouse aortas. The authors also thank J. Remis for CryoTEM assistance and the following facilities at Northwestern University: Robert H. Lurie Comprehensive Cancer Center Flow Cytometry Core; Center for Advanced Molecular Imaging; Biological imaging facility; Mouse Histology and Phenotyping Laboratory; Biological imaging facility and Keck-II facility of Northwestern University's NUANCE Center. This research was supported by the National Science Foundation CAREER Award (grant no. 1453576), the National Institutes of Health Director's New Innovator Award (grant no. 1DP2HL132390-01), American Heart Association (AHA) Postdoctoral Fellowship (17POST33670713), and the Louis A. Simpson & Kimberly K. Querrey Center for Regenerative Nanomedicine Regenerative Nanomedicine Catalyst Award. Publisher Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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

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DO - 10.1002/adfm.201904399

M3 - Article

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VL - 29

JO - Advanced Functional Materials

JF - Advanced Functional Materials

IS - 42

M1 - 1904399

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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