Immune cell screening of a nanoparticle library improves atherosclerosis therapy Academic Article uri icon

Overview

MeSH Major

  • Brain Stem Neoplasms
  • Glioma
  • Positron-Emission Tomography

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.

publication date

  • November 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5098679

Digital Object Identifier (DOI)

  • 10.1073/pnas.1609629113

PubMed ID

  • 27791119

Additional Document Info

start page

  • E6731

end page

  • E6740

volume

  • 113

number

  • 44