Multivalent viral capsids with internal cargo for fibrin imaging.
Allie C Obermeyer1, Stacy L Capehart1, John B Jarman1
1Department of Chemistry, University of California, Berkeley, California, United States of America.
Chemically functionalized bacteriophage MS2 capsids were developed as targeted nanoparticles for fibrin imaging. These novel nanocarriers effectively bind to fibrin clots, showing potential for improved thrombosis detection and treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Imaging
Background:
- Thrombosis is a major cause of cardiovascular diseases like myocardial infarction and stroke.
- Targeted imaging agents can offer molecular insights into pathological clots for better diagnosis and therapy.
- Nanocarriers are versatile platforms for developing targeted molecular imaging agents.
Purpose of the Study:
- To synthesize and evaluate chemically functionalized bacteriophage MS2 capsids as biomolecule-based nanoparticles for fibrin imaging.
- To assess the efficacy of MS2 capsids functionalized with fibrin-targeting peptides for clot detection.
Main Methods:
- MS2 capsids were chemically modified via oxidative coupling to conjugate approximately 90 fibrin-targeting peptides per capsid.
- The impact of targeted capsids on thrombin-mediated clot formation was assessed in vitro.
- Near-infrared fluorophores were installed on the interior surface for optical detection of fibrin binding.
Main Results:
- Multivalent, targeted MS2 capsids demonstrated superior inhibition of clot formation compared to free peptides, with a ten-fold lower effective concentration.
- Targeted capsids showed specific binding to fibrin clots, achieving higher signal-to-background ratios than non-targeted controls.
- Optical detection confirmed the binding of functionalized capsids to fibrin.
Conclusions:
- Chemically functionalized MS2 capsids serve as effective nanocarriers for targeting fibrin.
- These targeted nanocarriers show promise for in vitro diagnostic applications in thrombosis.
- Fibrin-targeted MS2 capsids could potentially be utilized as delivery agents for thrombi in future therapeutic strategies.
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