1. Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species.
- Author
-
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, Pérez-Medina C, and Mulder WJM
- Subjects
- Animals, Apolipoproteins E deficiency, Atherosclerosis diagnostic imaging, Atherosclerosis drug therapy, Disease Models, Animal, Female, Lipoproteins, HDL metabolism, Lipoproteins, HDL toxicity, Magnetic Resonance Imaging, Male, Mice, Inbred C57BL, Positron-Emission Tomography, Rabbits, Simvastatin pharmacology, Simvastatin therapeutic use, Species Specificity, Swine, Tissue Distribution, Atherosclerosis immunology, Atherosclerosis therapy, Imaging, Three-Dimensional, Immunotherapy, Nanomedicine
- 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., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2019
- Full Text
- View/download PDF