Development of Nanomedicine for the Treatment of Cardiovascular Diseases

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(1)We have demonstrated that intravenous administration of NK911, a nanoparticle containing antiproliferative drug, NK911, selectivelyaccumulates in the balloon-injured vascular lesion without endothelium and releases doxorubicin, an anti-proliferative agent, at a higher concentration.(2)We have then demonstrated that intravenous administration of NK911 immediately after and 3 and 6 days after balloon injury markedly suppresses the development of vascular lesions at 4 weeks after the procedure in the rat carotid artery. Importantly, no adverse effects, such as weight loss, hematological disorder, and liver dysfunction, were noted. These results suggest that nano-therapy with NK911 is a promising strategy for the prevention of restenosis after percutaneous coronary intervention(PCI).(3)We have developed a new stent that is coated with endothelial progenitor cells on it. We have confirmed that with this new stent, vascular re-endothelialization is enhanced as compared with a conventional stent.(4)We have developed a new MRI contrast medium that detects the de-endothelialized vascular lesion. This concept is based on the observation that Evans-blue selectively accumulates into the de-endothelialized lesion. With this new contrast medium we have demonstrated that we are able to detect the de-endothelialized lesion in the rat carotid artery in vivo.