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Hepatology:纳米粒子的靶向递送对肝细胞癌的神奇作用!

2017-11-08 MedSci MedSci原创

肝细胞癌(HCC)是一种侵袭性肿瘤,目前的治疗方式主要为有限的系统性和局部性治疗。尽管基于microRNA(miRNA)的疗法具有显着的潜力,但其靶向递送仍然是目前治疗的主要挑战。 miR-199a-3p在HCC中起着重要的肿瘤抑制剂作用,其调节各种细胞生长过程。近来,基于肽的纳米颗粒(NP)已经被开发用于递送包括miRNA的寡核苷酸。近期,一项发表在杂志Hepatology上的研究描述

肝细胞癌(HCC)是一种侵袭性肿瘤,目前的治疗方式主要为有限的系统性和局部性治疗。尽管基于microRNA(miRNA)的疗法具有显着的潜力,但其靶向递送仍然是目前治疗的主要挑战。 


miR-199a-3p在HCC中起着重要的肿瘤抑制剂作用,其调节各种细胞生长过程。近来,基于肽的纳米颗粒(NP)已经被开发用于递送包括miRNA的寡核苷酸。

近期,一项发表在杂志Hepatology上的研究描述了可以选择性递送miR-199a-3p以恢复失调的基因表达的HCC的精氨酸α,β-脱氢苯丙氨酸(RΔF)纳米粒子的合成和表征。

靶向递送是通过将乳糖酸(LA)与已知在HCC细胞系中过表达的无唾液酸糖蛋白受体的配体RΔFNps(RΔF-LA NPs)缀合而实现的。RΔF-LA NPs浓缩miR-199a-3p至平均大小约为60nm,ζ电位约为+2.54mV。

研究发现RΔF-LA/miR NP可以在血清中稳定并针对RNase攻击。RΔF-LA/miR NP显示细胞摄取增强以及对miR-199a-3p的有效递送,最终导致miR-199a-3p水平(超过500倍)的显着增加。

增加的miR-199a-3p水平显着抑制细胞增殖和迁移,并诱导细胞凋亡和体外特异性靶基因(mTOR)的下调。

将其静脉注射至携带HCC肿瘤的裸鼠后,RΔF-LA / miR NPs显示出高肿瘤/低器官比率。RΔF-LA / miR NPs处理的小鼠表现出肿瘤生长下降> 50%,这也与抑制mTOR蛋白表达、肿瘤细胞增殖以及存活率提高(p <0.0.5)相一致。

此项研究结果表明:RΔF-LA/miR NP显示显着增强的miRNA递送,这强调了其作为HCC治疗方法的发展潜力。

原始出处:
Varshney A, Panda JJ, et al. Targeted delivery of miR-199a-3p using self-assembled dipeptide nanoparticles efficiently reduces hepatocellular carcinoma. Hepatology. 2017 Nov 6. doi: 10.1002/hep.29643. 

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    2018-08-02 xjy02
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    2017-11-10 gwc384
  5. [GetPortalCommentsPageByObjectIdResponse(id=1978601, encodeId=af6a19e86016c, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Sep 08 03:59:00 CST 2018, time=2018-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863320, encodeId=a5f21863320c3, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Thu Aug 02 00:59:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772941, encodeId=4bfb1e7294132, content=<a href='/topic/show?id=89f3e742947' target=_blank style='color:#2F92EE;'>#纳米粒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77429, encryptionId=89f3e742947, topicName=纳米粒)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e8ae38449394, createdName=zjubiostat, createdTime=Fri Jan 19 12:59:00 CST 2018, time=2018-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426883, encodeId=8d8a14268838e, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Fri Nov 10 10:59:00 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580620, encodeId=08491580620c9, content=<a href='/topic/show?id=d4c6e7430be' target=_blank style='color:#2F92EE;'>#纳米粒子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77430, encryptionId=d4c6e7430be, topicName=纳米粒子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eedc16636878, createdName=ms920641618706883, createdTime=Fri Nov 10 10:59:00 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260244, encodeId=d01c2602449a, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Nov 10 09:23:42 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259803, encodeId=0cd125980328, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Nov 08 21:32:28 CST 2017, time=2017-11-08, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1978601, encodeId=af6a19e86016c, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Sep 08 03:59:00 CST 2018, time=2018-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863320, encodeId=a5f21863320c3, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Thu Aug 02 00:59:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772941, encodeId=4bfb1e7294132, content=<a href='/topic/show?id=89f3e742947' target=_blank style='color:#2F92EE;'>#纳米粒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77429, encryptionId=89f3e742947, topicName=纳米粒)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e8ae38449394, createdName=zjubiostat, createdTime=Fri Jan 19 12:59:00 CST 2018, time=2018-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426883, encodeId=8d8a14268838e, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Fri Nov 10 10:59:00 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580620, encodeId=08491580620c9, content=<a href='/topic/show?id=d4c6e7430be' target=_blank style='color:#2F92EE;'>#纳米粒子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77430, encryptionId=d4c6e7430be, topicName=纳米粒子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eedc16636878, createdName=ms920641618706883, createdTime=Fri Nov 10 10:59:00 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260244, encodeId=d01c2602449a, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Nov 10 09:23:42 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259803, encodeId=0cd125980328, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Nov 08 21:32:28 CST 2017, time=2017-11-08, status=1, ipAttribution=)]
    2017-11-10 大爰

    学习并分享!!

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1978601, encodeId=af6a19e86016c, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Sep 08 03:59:00 CST 2018, time=2018-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863320, encodeId=a5f21863320c3, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Thu Aug 02 00:59:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772941, encodeId=4bfb1e7294132, content=<a href='/topic/show?id=89f3e742947' target=_blank style='color:#2F92EE;'>#纳米粒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77429, encryptionId=89f3e742947, topicName=纳米粒)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e8ae38449394, createdName=zjubiostat, createdTime=Fri Jan 19 12:59:00 CST 2018, time=2018-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426883, encodeId=8d8a14268838e, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Fri Nov 10 10:59:00 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580620, encodeId=08491580620c9, content=<a href='/topic/show?id=d4c6e7430be' target=_blank style='color:#2F92EE;'>#纳米粒子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77430, encryptionId=d4c6e7430be, topicName=纳米粒子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eedc16636878, createdName=ms920641618706883, createdTime=Fri Nov 10 10:59:00 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=260244, encodeId=d01c2602449a, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Nov 10 09:23:42 CST 2017, time=2017-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=259803, encodeId=0cd125980328, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Nov 08 21:32:28 CST 2017, time=2017-11-08, status=1, ipAttribution=)]
    2017-11-08 1ddf0692m34(暂无匿称)

    学习了.涨知识

    0

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