Development of Nanotechnology Based Less Invasive Therapy for Vein Graft Failure

基于纳米技术的静脉移植失败微创疗法的开发

• 批准号: 20790992
• 负责人: KIMURA Satoshi
• 金额: $ 2.75万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790992/
• 关键词: 心臓大血管外科学; ナノテクノロジー; 静脈グラフト

BACKGROUND : Clinical outcome of surgical revascularization using autologous vein graft is limited by vein graft failure attributable to neointima formation. Platelet-derived growth factor (PDGF) plays a central role in the pathogenesis of vein graft failure. Therefore, we hypothesized that nanoparticle (NP)-mediated drug delivery system of PDGF-receptor (PDGF-R) tyrosine kinase inhibitor (imatinib mesylate: STI571) could be an innovative therapeutic strategy. METHODS AND RESULTS: Uptake of STI571-NP normalized PDGF-induced cell proliferation and migration. Excised rabbit jugular vein was treated ex vivo with PBS, STI571 only, FITC-NP, or STI571-NP, then interposed back into the carotid artery position. NP was detected in many cells in the neointima and media at 7 and 28 days after grafting. Significant neointima was formed 28 days after grafting in the PBS group; this neointima formation was suppressed in the STI571-NP group. STI571-NP treatment inhibited cell proliferation and phosphorylation of the PDGF-R-beta but did not affect inflammation and endothelial regeneration. CONCLUSIONS: STI571-NP-induced suppression of vein graft neointima formation holds promise as a strategy for preventing vein graft failure.

背景：使用自体静脉移植物进行外科血运重建的临床结果受到移植静脉失败的限制，这些失败可归因于新生内膜的形成。血小板衍生生长因子(PDGF)在静脉移植失败的发病机制中起核心作用。因此，我们推测纳米粒(NP)介导的PDGF受体(PDGF-R)酪氨酸激酶抑制剂药物传递系统(伊马替尼：STI571)可能是一种创新的治疗策略。方法和结果：正常摄取STI571-NP可使PDGF诱导的细胞增殖和迁移。离体兔颈静脉分别用PBS、STI571、FITC-NP或STI571-NP处理，然后插回到颈动脉位置。移植后7天和28天，新生内膜和中膜中有大量细胞表达NP。移植后28天，PBS组有明显的新生内膜形成；STI571-NP组这种新生内膜的形成被抑制。STI571-NP处理抑制细胞增殖和PDGF-R-β的磷酸化，但不影响炎症和内皮再生。结论：STI571-NP诱导的抑制移植静脉新生内膜形成有望成为预防移植静脉失败的一种策略。

项目成果

Nanoparticle-Mediated Delivery of Nuclear Factor κ_B Decoy Into Lungs Ameliorates Monocrotaline-Induced Pulmonary Arterial.

纳米颗粒介导的核因子 κ_B 诱饵进入肺部可改善野百合碱诱导的肺动脉。

• 发表时间: 2009
• 期刊: Hypertension. 53(5)
• 作者: Kimura S;et al.
• 通讯作者: et al.

Single Intratracheal Instillation of Bioabsorbable Nanoparticle Incorporated with Statin Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Improved Survival-An Innovative Therapeutic Approach for Pulmonary Arterial Hypertension-

单次气管内滴注掺有他汀类药物的生物可吸收纳米颗粒可改善野百合碱诱导的肺动脉高压并提高生存率-肺动脉高压的创新治疗方法-

• 发表时间: 2009
• 作者: Chen L;et al.
• 通讯作者: et al.

Formulation of nanoparticle-eluting stents by a cationic electrodeposit coating technology: Efficient and safe nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries.

采用阳离子电沉积涂层技术配制纳米颗粒洗脱支架：通过生物可吸收聚合物纳米颗粒洗脱支架在猪冠状动脉中高效、安全地输送纳米药物。

• 发表时间: 2009
• 期刊: J Am Coll Cardiol : Cardovasular Intervention. 2(4)
• 作者: Nakano K;Egashira K;Masuda S;Funakoshi K;Zhao G;Kimura S;Matoba T;Sueishi K;Endo Y;Kawashima Y;Hara K;Tsujimoto H;Tominaga R;Sunagawa K
• 通讯作者: Sunagawa K

Formulation of nanoparticle-eluting stents by a cationic electrodeposit coating technology : Efficient and safe nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries.

通过阳离子电沉积涂层技术配制纳米颗粒洗脱支架：通过生物可吸收聚合物纳米颗粒洗脱支架在猪冠状动脉中高效安全地输送纳米药物。

• 发表时间: 2009
• 期刊: JACC : Cardiovascular Intervention 2(4)
• 作者: Nakano K;et al.
• 通讯作者: et al.

Formulation of Nanoparticle-Eluting Stents by a Cationic Electrodeposition Coating Technology Efficient Nano-Drug Delivery via Bioabsorbable Polymeric Nanoparticle-Eluting Stents in Porcine Coronary Arteries

• DOI: 10.1016/j.jcin.2008.08.023
• 发表时间: 2009-04-01
• 期刊: JACC-CARDIOVASCULAR INTERVENTIONS
• 影响因子: 11.3
• 作者: Nakano, Kaku;Egashira, Kensuke;Sunagawa, Kenji
• 通讯作者: Sunagawa, Kenji