| Literature DB >> 27791119 |
Jun Tang1,2, Samantha Baxter1, Arjun Menon3, Amr Alaarg1,4, Brenda L Sanchez-Gaytan1, Francois Fay1, Yiming Zhao1, Mireille Ouimet3, Mounia S Braza1, Valerie A Longo5, Dalya Abdel-Atti2, Raphael Duivenvoorden1, Claudia Calcagno1, Gert Storm4,6, Sotirios Tsimikas7, Kathryn J Moore3, Filip K Swirski8, Matthias Nahrendorf8, Edward A Fisher3, Carlos Pérez-Medina1, Zahi A Fayad1, Thomas Reiner2, Willem J M Mulder9,10.
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.Entities:
Keywords: atherosclerosis; drug delivery; immunotherapy; molecular imaging; nanomedicine
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Year: 2016 PMID： 27791119 PMCID： PMC5098679 DOI： 10.1073/pnas.1609629113
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205