Development of Nanomedicine for the Treatment of Cardiovascular Diseases

开发治疗心血管疾病的纳米药物

• 批准号: 13557068
• 负责人: SHIMOKAWA Hiroaki
• 金额: $ 8.83万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557068/
• 关键词: Nanotechnology; Nanocapsule; Nanomedicine; Functioning contrast medium; Nanodiagnosis; バルーン傷害; 再狭窄; サイトカイン; ナノカプセル(粒子); 冠動脈インターベンション; 虚血性心臓病

(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.

(1)我们已经证明，静脉注射NK911（一种含有抗增殖药物NK911的纳米颗粒）可以选择性地在球囊损伤的无内皮血管病变中积聚，并以更高的浓度释放出抗增殖剂阿霉素。(2)我们然后证明，在球囊损伤后立即以及3天和6天静脉注射NK911可显着抑制血管病变的发展大鼠颈动脉手术后 4 周。重要的是，没有发现任何副作用，例如体重减轻、血液系统疾病和肝功能障碍。这些结果表明，NK911纳米疗法是预防经皮冠状动脉介入治疗（PCI）后再狭窄的一种有前途的策略。（3）我们开发了一种新型支架，其上涂有内皮祖细胞。我们已经证实，与传统支架相比，这种新型支架可以增强血管再内皮化。(4)我们开发了一种新的 MRI 造影剂，可以检测去内皮化的血管病变。这个概念基于伊文思蓝选择性积累到去内皮化病变中的观察。使用这种新的造影剂，我们已经证明我们能够在体内检测大鼠颈动脉中的去内皮化病变。

项目成果

Shirota T, Yasui H, Shimokawa H, Matsuda T.: "Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in vitro endothelialization on hydbrid vascular tissue."Biomaterials. 24. 2295-2302 (2003)

Shirota T、Yasui H、Shimokawa H、Matsuda T.：“内皮祖细胞 (EPC) 接种的血管内支架装置的制造和混合血管组织的体外内皮化。”生物材料。

Uwatoku T, Shimokawa H. et al.: "Application of nanoparticle technology for the Prevention of restenosis after balloon injury In rats."Circulation Research. 92. e63-e69 (2003)

Uwatoku T、Shimokawa H. 等人：“纳米粒子技术在预防大鼠球囊损伤后再狭窄中的应用。”循环研究。

Shirota T, Yasui H, Shimokawa H, Matsuda T: "Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in"Biomaterials. 24. 2295-2302 (2003)

Shirota T、Yasui H、Shimokawa H、Matsuda T：“内皮祖细胞 (EPC) 接种的血管内支架装置的制造和”生物材料。

Yamamoto T, Shimokawa H, Katayama Y.: "First functionalized MRI contrast agent recognizing vascular lesions."Analytical Sciences. 20. 5-7 (2004)

Yamamoto T、Shimokawa H、Katayama Y.：“第一个识别血管病变的功能化 MRI 造影剂。”分析科学。

Shimokawa H: "Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases"Journal of Cardiovascular Pharmacology. (in press). (2002)

Shimokawa H：“Rho激酶作为治疗心血管疾病的新型治疗靶点”心血管药理学杂志。