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)We已经证明静脉内施用NK911，一种含有抗增殖药物NK911的纳米颗粒，选择性地在没有内皮的球囊损伤的血管病变中积聚，并以更高浓度释放多柔比星，一种抗增殖剂。(2)We然后证明了在球囊损伤后立即和3和6天后静脉内施用NK 911显著抑制了大鼠颈动脉中在手术后4周的血管损伤的发展。重要的是，未观察到不良反应，如体重减轻、血液学疾病和肝功能障碍。这些结果表明，NK911纳米治疗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)We已经开发了一种新的支架，其上涂覆有内皮祖细胞。我们已经证实，与传统支架相比，这种新支架增强了血管再内皮化。(4)We开发了一种新的MRI造影剂，可检测去内皮化血管病变。这一概念是基于埃文斯蓝选择性地积聚到去内皮化病变中的观察结果。使用这种新的造影剂，我们已经证明，我们能够检测在体内大鼠颈动脉的去内皮化病变。

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。

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。

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。