DTPA-coupled anti-elastin-targeted nanoparticles resulted in significant regression of ex vivo porcine aortic valve calcifications compared to IgG-NP control without affecting cellular viability.
Do DTPA-coupled anti-elastin-targeted nanoparticles reduce calcification in ex vivo porcine aortic valves compared to IgG-NP controls?
Elastin-targeted nanoparticles delivering DTPA can effectively reverse calcification in ex vivo porcine aortic valves without compromising cell viability, representing a potential future non-surgical approach for calcific aortic valve disease.
Calcified aortic valve disease in its final stage leads to aortic valve stenosis, limiting cardiac function. To date, surgical intervention is the only option for treating calcific aortic valve stenosis. This study combined controlled drug delivery by nanoparticles (NPs) and active targeting by antibody conjugation. The chelating agent diethylenetriaminepentaacetic acid (DTPA) was covalently bound to human serum albumin (HSA)-based NP, and the NP surface was modified using conjugating antibodies (anti-elastin or isotype IgG control). Calcification was induced ex vivo in porcine aortic valves by preincubation in an osteogenic medium containing 2.5 mM sodium phosphate for five days. Valve calcifications mainly consisted of basic calcium phosphate crystals. Calcifications were effectively resolved by adding 1-5 mg DTPA/mL medium. Incubation with pure DTPA, however, was associated with a loss of cellular viability. Reversal of calcifications was also achieved with DTPA-coupled anti-elastin-targeted NPs containing 1 mg DTPA equivalent. The addition of these NPs to the conditioned media resulted in significant regression of the valve calcifications compared to that in the IgG-NP control without affecting cellular viability. These results represent a step further toward the development of targeted nanoparticular formulations to dissolve aortic valve calcifications.
Feldmann et al. (Fri,) conducted a other in Calcified aortic valve disease. DTPA-coupled anti-elastin-targeted nanoparticles vs. IgG-NP control was evaluated on Regression of valve calcifications. DTPA-coupled anti-elastin-targeted nanoparticles resulted in significant regression of ex vivo porcine aortic valve calcifications compared to IgG-NP control without affecting cellular viability.