An anti-PDGFRβ aptamer for selective delivery of small therapeutic peptide to cardiac cells
Articolo
Data di Pubblicazione:
2018
Citazione:
An anti-PDGFRβ aptamer for selective delivery of small therapeutic peptide to cardiac cells / A. Romanelli, A. A., A. C., C. S., C. P., I. M., M. J., C. G., C. D.. - In: PLOS ONE. - ISSN 1932-6203. - 13:3(2018 Mar), pp. e0193392.1-e0193392.9. [10.1371/journal.pone.0193392]
Abstract:
Small therapeutic peptides represent a promising field for the treatment of pathologies such as cardiac diseases. However, the lack of proper target-selective carriers hampers their translation towards a potential clinical application. Aptamers are cell-specific carriers that bind with high affinity to their specific target. However, some limitations on their conjugation to small peptides and the functionality of the resulting aptamer-peptide chimera exist. Here, we generated a novel aptamer-peptide chimera through conjugation of the PDGFRβ-targeting Gint4.T aptamer to MP a small mimetic peptide that via targeting of the Cavβ2 subunit of the L-type calcium channel (LTCC) can recover myocardial function in pathological heart conditions associated with defective LTCC function. The conjugation reaction was performed by click chemistry in the presence of N,N,N′,N′,N″-pentamethyldiethylenetriamine as a Cu (I) stabilizing agent in a DMSO-free aqueous buffer. When administered to cardiac cells, the Gint4.T-MP aptamer-peptide chimera was successfully internalized in cells, allowing the functional targeting of MP to LTCC. This approach represents the first example of the use of an internalizing aptamer for selective delivery of a small therapeutic peptide to cardiac cells.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Blotting, Western; Calcium; Calcium Channels, L-Type; Cardiovascular Agents; Cell Line; Click Chemistry; Intracellular Space; Mice; Myocytes, Cardiac; Peptides; Protein Stability; Voltage-Sensitive Dye Imaging; Water; Aptamers, Nucleotide; Drug Carriers; Receptor, Platelet-Derived Growth Factor beta; Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
Elenco autori:
A. Romanelli, A. A., A. C., C. S., C. P., I. M., M. J., C. G., C. D.
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