Title | Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Binderup T, Duivenvoorden R, Fay F, van Leent MMT, Malkus J, Baxter S, Ishino S, Zhao Y, Sanchez-Gaytan B, Teunissen AJP, Frederico YCA, Tang J, Carlucci G, Lyashchenko S, Calcagno C, Karakatsanis N, Soultanidis G, Senders ML, Robson PM, Mani V, Ramachandran S, Lobatto ME, Hutten BA, Granada JF, Reiner T, Swirski FK, Nahrendorf M, Kjaer A, Fisher EA, Fayad ZA, PĂ©rez-Medina C, Mulder WJM |
Journal | Sci Transl Med |
Volume | 11 |
Issue | 506 |
Date Published | 2019 08 21 |
ISSN | 1946-6242 |
Keywords | Animals, Apolipoproteins E, Atherosclerosis, Disease Models, Animal, Female, Imaging, Three-Dimensional, Immunotherapy, Lipoproteins, HDL, Magnetic Resonance Imaging, Male, Mice, Inbred C57BL, Nanomedicine, Positron-Emission Tomography, Rabbits, Simvastatin, Species Specificity, Swine, Tissue Distribution |
Abstract | Nanomedicine research produces hundreds of studies every year, yet very few formulations have been approved for clinical use. This is due in part to a reliance on murine studies, which have limited value in accurately predicting translational efficacy in larger animal models and humans. Here, we report the scale-up of a nanoimmunotherapy from mouse to large rabbit and porcine atherosclerosis models, with an emphasis on the solutions we implemented to overcome production and evaluation challenges. Specifically, we integrated translational imaging readouts within our workflow to both analyze the nanoimmunotherapeutic's in vivo behavior and assess treatment response in larger animals. We observed our nanoimmunotherapeutic's anti-inflammatory efficacy in mice, as well as rabbits and pigs. Nanoimmunotherapy-mediated reduction of inflammation in the large animal models halted plaque progression, supporting the approach's translatability and potential to acutely treat atherosclerosis. |
DOI | 10.1126/scitranslmed.aaw7736 |
Alternate Journal | Sci Transl Med |
PubMed ID | 31434756 |
PubMed Central ID | PMC7328283 |
Grant List | R01 HL125703 / HL / NHLBI NIH HHS / United States R01 HL144072 / HL / NHLBI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 EB009638 / EB / NIBIB NIH HHS / United States R01 HL118440 / HL / NHLBI NIH HHS / United States R01 HL071021 / HL / NHLBI NIH HHS / United States P01 HL131478 / HL / NHLBI NIH HHS / United States |