Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Jun Tang; Samantha Baxter; Arjun Menon; Amr Alaarg; Brenda L. Sanchez-Gaytan; Francois Fay; Yiming Zhao; Mireille Ouimet; Mounia S. Braza; Valerie A. Longo; Dalya Abdel-Atti; Raphael Duivenvoorden; Claudia Calcagno; Gert Storm; Sotirios Tsimikas; Kathryn J. Moore; Filip K. Swirski; Matthias Nahrendorf; Edward A. Fisher; Carlos Pérez-Medina; Zahi A. Fayad; Thomas Reiner; Willem J.M. Mulder

doi:10.1073/pnas.1609629113

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Jun Tang
, Samantha Baxter
, Arjun Menon
, Amr Alaarg
, Brenda L. Sanchez-Gaytan
, Francois Fay
, Yiming Zhao
, Mireille Ouimet
, Mounia S. Braza
, Valerie A. Longo
, Dalya Abdel-Atti
, Raphael Duivenvoorden
, Claudia Calcagno
, Gert Storm
, Sotirios Tsimikas
, Kathryn J. Moore
, Filip K. Swirski
, Matthias Nahrendorf
, Edward A. Fisher
, Carlos Pérez-Medina

Zahi A. Fayad, Thomas Reiner, Willem J.M. Mulder

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

108 Scopus citations

Abstract

Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library's nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis, we quantitatively evaluated the library's immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases.

Original language	English
Pages (from-to)	E6731-E6740
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	44
DOIs	https://doi.org/10.1073/pnas.1609629113
State	Published - 1 Nov 2016

Keywords

Atherosclerosis
Drug delivery
Immunotherapy
Molecular imaging
Nanomedicine

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10.1073/pnas.1609629113

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Tang, J., Baxter, S., Menon, A., Alaarg, A., Sanchez-Gaytan, B. L., Fay, F., Zhao, Y., Ouimet, M., Braza, M. S., Longo, V. A., Abdel-Atti, D., Duivenvoorden, R., Calcagno, C., Storm, G., Tsimikas, S., Moore, K. J., Swirski, F. K., Nahrendorf, M., Fisher, E. A., ... Mulder, W. J. M. (2016). Immune cell screening of a nanoparticle library improves atherosclerosis therapy. Proceedings of the National Academy of Sciences of the United States of America, 113(44), E6731-E6740. https://doi.org/10.1073/pnas.1609629113

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title = "Immune cell screening of a nanoparticle library improves atherosclerosis therapy",

abstract = "Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library's nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis, we quantitatively evaluated the library's immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases.",

keywords = "Atherosclerosis, Drug delivery, Immunotherapy, Molecular imaging, Nanomedicine",

author = "Jun Tang and Samantha Baxter and Arjun Menon and Amr Alaarg and Sanchez-Gaytan, \{Brenda L.\} and Francois Fay and Yiming Zhao and Mireille Ouimet and Braza, \{Mounia S.\} and Longo, \{Valerie A.\} and Dalya Abdel-Atti and Raphael Duivenvoorden and Claudia Calcagno and Gert Storm and Sotirios Tsimikas and Moore, \{Kathryn J.\} and Swirski, \{Filip K.\} and Matthias Nahrendorf and Fisher, \{Edward A.\} and Carlos P{\'e}rez-Medina and Fayad, \{Zahi A.\} and Thomas Reiner and Mulder, \{Willem J.M.\}",

note = "Publisher Copyright: {\textcopyright} 2016 by the authors; licensee MDPI, Basel, Switzerland.",

year = "2016",

month = nov,

day = "1",

doi = "10.1073/pnas.1609629113",

language = "English",

volume = "113",

pages = "E6731--E6740",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Tang, J, Baxter, S, Menon, A, Alaarg, A, Sanchez-Gaytan, BL, Fay, F, Zhao, Y, Ouimet, M, Braza, MS, Longo, VA, Abdel-Atti, D, Duivenvoorden, R, Calcagno, C, Storm, G, Tsimikas, S, Moore, KJ, Swirski, FK, Nahrendorf, M, Fisher, EA, Pérez-Medina, C, Fayad, ZA, Reiner, T & Mulder, WJM 2016, 'Immune cell screening of a nanoparticle library improves atherosclerosis therapy', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 44, pp. E6731-E6740. https://doi.org/10.1073/pnas.1609629113

TY - JOUR

T1 - Immune cell screening of a nanoparticle library improves atherosclerosis therapy

AU - Tang, Jun

AU - Baxter, Samantha

AU - Menon, Arjun

AU - Alaarg, Amr

AU - Sanchez-Gaytan, Brenda L.

AU - Fay, Francois

AU - Zhao, Yiming

AU - Ouimet, Mireille

AU - Braza, Mounia S.

AU - Longo, Valerie A.

AU - Abdel-Atti, Dalya

AU - Duivenvoorden, Raphael

AU - Calcagno, Claudia

AU - Storm, Gert

AU - Tsimikas, Sotirios

AU - Moore, Kathryn J.

AU - Swirski, Filip K.

AU - Nahrendorf, Matthias

AU - Fisher, Edward A.

AU - Pérez-Medina, Carlos

AU - Fayad, Zahi A.

AU - Reiner, Thomas

AU - Mulder, Willem J.M.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library's nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis, we quantitatively evaluated the library's immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases.

AB - Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library's nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis, we quantitatively evaluated the library's immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases.

KW - Atherosclerosis

KW - Drug delivery

KW - Immunotherapy

KW - Molecular imaging

KW - Nanomedicine

UR - https://www.scopus.com/pages/publications/84994005220

U2 - 10.1073/pnas.1609629113

DO - 10.1073/pnas.1609629113

M3 - Article

C2 - 27791119

AN - SCOPUS:84994005220

SN - 0027-8424

VL - 113

SP - E6731-E6740

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 44

ER -

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Abstract

Keywords

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