Investigating the In Vivo Biodistribution of Extracellular Vesicles Isolated from Various Human Cell Sources Using Positron Emission Tomography

• DOI: 10.1021/acs.molpharmaceut.4c00298
• Publication Date: 2024-08-22T03:30:39Z
• Authors: Zachary T. Rosenk...; Anna S. Thickens; John A. Kink; Eduardo Aluicio-S...; Jonathan W. Engle; Peiman Hematti; Reinier Hernandez
• Keywords: Biodistribution; Ex vivo

Positron emission tomography (PET) is a powerful tool for investigating the in vivo behavior of drug delivery systems. We aimed to assess biodistribution extracellular vesicles (EVs), nanosized secreted by cells isolated from various human cell sources using PET. EVs were mesenchymal stromal (MSCs) (MSC EVs), macrophages (Mϕ and melanoma line (A375 EVs) centrifugation conjugated with deferoxamine radiolabeling Zr-89. PET radiolabeled evaluated their tissue tropisms. Our study also investigated differences mouse models, utilizing immunocompetent immunocompromised mice an A375 xenograft tumor model. Lastly, we impact different labeling techniques on observed EV biodistribution, including covalent surface modification membrane incorporation. showed that all tested exhibited extended circulation generally low uptake liver, spleen, lungs. However, Mϕ high liver uptake, potentially attributable intrinsic tropism these protein composition. MSC differed between immunodeficient mice, increased spleen latter. xenografts demonstrated efficient EVs, but no preferential tissue-specific was found. Biodistribution surface-conjugated had blood lung compared integration. This demonstrates potential as effective carriers diseases, highlights importance selecting appropriate EV-based delivery, suggests can be harnessed optimize therapeutic efficacy. findings indicate cellular source technique, animal model influence biodistribution.