Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species

影像辅助纳米免疫疗法在多种动物动脉粥样硬化中的应用

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作者:Tina Binderup ,Raphaël Duivenvoorden ,Francois Fay ,Mandy M T van Leent ,Joost Malkus ,Samantha Baxter ,Seigo Ishino ,Yiming Zhao ,Brenda Sanchez-Gaytan ,Abraham J P Teunissen ,Yohana C A Frederico ,Jun Tang ,Giuseppe Carlucci ,Serge Lyashchenko ,Claudia Calcagno ,Nicolas Karakatsanis ,Georgios Soultanidis ,Max L Senders ,Philip M Robson ,Venkatesh Mani ,Sarayu Ramachandran ,Mark E Lobatto ,Barbara A Hutten ,Juan F Granada ,Thomas Reiner ,Filip K Swirski ,Matthias Nahrendorf ,Andreas Kjaer ,Edward A Fisher ,Zahi A Fayad ,Carlos Pérez-Medina ,Willem J M Mulder

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.

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