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Nature Chemical Biology:新型NO靶向递送系统 为治疗血管损伤提供新策略

2019-01-15 佚名 南开新闻网

一氧化氮(NO)是心血管系统的一个重要气体信号分子,在维持血管正常生理功能中发挥重要作用,并对血管稳态进行精密调控。人们所熟知的经典心血管药物——硝酸甘油,就是通过释放一氧化氮发挥扩张血管作用的。但是,过高剂量的NO会导致细胞凋亡,产生毒性。如果NO全身性释放还会导致血压下降、心跳加速等副作用。因此,发展精准的NO递送系统,实现靶向传输是目前该领域研究热点,也是制约NO生物材料临床应用的“瓶颈”。

一氧化氮(NO)是血管系统的一个重要气体信号分子,在维持血管正常生理功能中发挥重要作用,并对血管稳态进行精密调控。人们所熟知的经典心血管药物——硝酸甘油,就是通过释放一氧化氮发挥扩张血管作用的。但是,过高剂量的NO会导致细胞凋亡,产生毒性。如果NO全身性释放还会导致血压下降、心跳加速等副作用。因此,发展精准的NO递送系统,实现靶向传输是目前该领域研究热点,也是制约NO生物材料临床应用的“瓶颈”。

经过4年科研攻关,南开大学生命科学学院赵强教授与药学院沈杰副教授、程剑松副教授联合研究团队,针对内源性半乳糖苷酶会引发一氧化氮供体化合物分解导致NO非特异性释放的问题,利用化学生物学“凸凹互补”的原理设计制备了新型NO靶向递送系统,可以将NO精准递送至病灶部位。这种新型的NO递送系统有效解决了内源性酶导致的NO非特性释放和由此引发的副作用。

“非特异性释放是指除了在病灶部分,在全身其它组织器官中都有一定释放,因此,会对人体产生毒副作用。而我们设计的新策略类似于在疾病部位建立了一个药物‘加工厂’,通过静脉输送前药,经血液循环送达病灶,加工产生一氧化氮,用于疾病治疗,实现精准靶向。”赵强说。

研究人员将这种“凸凹互补”的NO递送体系应用于大鼠下肢缺血和小鼠急性肾缺血(AKI)等疾病模型,精准的NO传输能够更有效地促进血管新生,恢复大鼠下肢的血流灌注,促进AKI小鼠的肾脏组织修复,并有效改善肾脏功能。他们进一步在内皮一氧化氮合酶基因敲除小鼠模型中验证了这个新型的NO递送系统的有效性。

“这些研究结果表明,新型NO递送系统及其生物材料可能为糖尿病、动脉粥样硬化等慢性疾病状态下的血管损伤提供新的治疗策略。”赵强说。

日前,介绍该研究工作的论文以长文形式在线发表于国际权威期刊《Nature Chemical Biology》。

原始出处:

Jingli Hou,et al.Targeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pair.Nature Chemical Biology.31 December 2018

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    2019-10-08 stfoxst
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17 12:02:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568557, encodeId=f460156855e6c, content=<a href='/topic/show?id=838794862d0' target=_blank style='color:#2F92EE;'>#递送系统#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94862, encryptionId=838794862d0, topicName=递送系统)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=68f115392320, createdName=lingaifan, createdTime=Thu Jan 17 12:02:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=358239, encodeId=5333358239b1, content=希望早日用于临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Tue Jan 15 21:19:52 CST 2019, time=2019-01-15, status=1, ipAttribution=)]
    2019-11-30 liye789132251
  5. 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17 12:02:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568557, encodeId=f460156855e6c, content=<a href='/topic/show?id=838794862d0' target=_blank style='color:#2F92EE;'>#递送系统#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94862, encryptionId=838794862d0, topicName=递送系统)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=68f115392320, createdName=lingaifan, createdTime=Thu Jan 17 12:02:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=358239, encodeId=5333358239b1, content=希望早日用于临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Tue Jan 15 21:19:52 CST 2019, time=2019-01-15, status=1, ipAttribution=)]
    2019-02-04 sunylz
  6. 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17 12:02:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568557, encodeId=f460156855e6c, content=<a href='/topic/show?id=838794862d0' target=_blank style='color:#2F92EE;'>#递送系统#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94862, encryptionId=838794862d0, topicName=递送系统)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=68f115392320, createdName=lingaifan, createdTime=Thu Jan 17 12:02:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=358239, encodeId=5333358239b1, content=希望早日用于临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Tue Jan 15 21:19:52 CST 2019, time=2019-01-15, status=1, ipAttribution=)]
  7. 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time=2019-01-15, status=1, ipAttribution=)]
  8. 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    2019-01-15 医者仁心5538

    希望早日用于临床

    0

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