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bioRxiv ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39185150

RESUMEN

Background: The pursuit of selective therapeutic delivery to target tissue types represents a key goal in the treatment of a range of adverse health issues, including diseases afflicting the heart. The development of new cardiac-specific ligands is a crucial step towards effectively targeting therapeutics to the heart. Methods: Utilizing an ex vivo and in vivo SELEX approaches, we enriched a library of 2'-fluoro modified aptamers for ventricular cardiomyocyte specificity. Lead candidates were identified from this library, and their binding and internalization into cardiomyocytes was evaluated in both ex vivo and in vivo mouse studies. Results: The ex vivo and in vivo SELEX processes generated an aptamer library with significant cardiac specificity over non-cardiac tissues such as liver and skeletal muscle. Our lead candidate aptamer from this library, CA1, demonstrates selective in vivo targeting and delivery of a fluorophore cargo to ventricular cardiomyocytes within the murine heart, while minimizing off-target localization to non-cardiac tissues, including the liver. By employing a novel RNase-based assay to evaluate aptamer interactions with cardiomyocytes, we discovered that CA1 predominantly internalizes into ventricular cardiomyocytes; conversely, another candidate CA41 primarily binds to the cardiomyocyte cell surface. Conclusions: These findings suggest that CA1 and CA41 have the potential to be promising candidates for targeted drug delivery and imaging applications in cardiac diseases.

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