Dynamic Biodistribution of Extracellular Vesicles <i>in Vivo</i> Using a Multimodal Imaging Reporter
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Résumé
Extracellular vesicles (EVs) are nanosized vesicles released by normal and diseased cells as a novel form of intercellular communication and can serve as an effective therapeutic vehicle for genes and drugs. Yet, much remains unknown about the in vivo properties of EVs such as tissue distribution, blood levels, and urine clearance, important parameters that will define their therapeutic effectiveness and potential toxicity. Here we combined Gaussia luciferase and metabolic biotinylation to create a sensitive EV reporter (EV-GlucB) for multimodal imaging in vivo, as well as monitoring of EV levels in the organs and biofluids ex vivo after administration of EVs. Bioluminescence and fluorescence-mediated tomography imaging on mice displayed a predominant localization of intravenously administered EVs in the spleen followed by the liver. Monitoring EV signal in the organs, blood, and urine further revealed that the EVs first undergo a rapid distribution phase followed by a longer elimination phase via hepatic and renal routes within six hours, which are both faster than previously reported using dye-labeled EVs. Moreover, we demonstrate systemically injected EVs can be delivered to tumor sites within an hour following injection. Altogether, we show the EVs are dynamically processed in vivo with accurate spatiotemporal resolution and target a number of normal organs as well as tumors with implications for disease pathology and therapeutic design.
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La notice
- Revue
- ACS Nano
- Thématique
- Extracellular vesicles in disease
- Domaine
- Biochemistry, Genetics and Molecular Biology
- Établissements canadiens
- —
- Organismes subventionnaires
- National Institute of Neurological Disorders and StrokeCanadian Institutes of Health ResearchNational Cancer InstituteVoices Against Brain Cancer
- Mots-clés
- BiodistributionIn vivoEx vivoBioluminescence imagingExtracellular vesiclesLuciferasePreclinical imagingDistribution (mathematics)Reporter geneBiotinylationPharmacologySpleenCell biologyChemistryPathologyBiomedical engineeringBiologyMedicineBiochemistryImmunologyTransfectionGene expressionGene
- Résumé présent dans OpenAlex
- oui