Nat Commun:脑肿瘤完全消失,纳米颗粒突破血脑屏障,极难治癌症迎来新希望

2020-11-14 生物世界 Bio生物世界

血脑屏障(BBB)是指脑毛细血管壁与神经胶质细胞形成的血浆与脑细胞之间的屏障和由脉络丛形成的血浆和脑脊液之间的屏障,仅允许特定类型的分子从血流进入大脑神经元和其他周围细胞。

血脑屏障(BBB)是指脑毛细血管壁与神经胶质细胞形成的血浆与脑细胞之间的屏障和由脉络丛形成的血浆和脑脊液之间的屏障,仅允许特定类型的分子从血流进入大脑神经元和其他周围细胞。

血脑屏障的存在,对于阻止有害物质由血液进入大脑具有重要意义,然而,血脑屏障同时也阻止了大多数小分子药物和大分子(例如肽,蛋白质和基于基因的药物)的转移,严重限制了神经中枢系统疾病(例如神经退行性疾病、脑肿瘤,脑部感染和中风等)的治疗。

胶质母细胞瘤(Glioblastoma),是最常见、最致命和最难以治疗的成人脑肿瘤(之一)。外科手术切除肿瘤,然后进行放射治疗和替莫唑胺给药治疗,是目前的治疗方案,但该方案仅能改善患者的整体生存率。胶质母细胞瘤患者目前的中位生存期仅为18个月,平均五年生存率低于5%。

2020年11月10日,美国密歇根大学的研究人员在 Nature 子刊 Nature Communications 杂志发表了题为:Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy 的研究论文。

研究团队开发出了基于具有细胞穿透肽iRGD的聚合人血清白蛋白(HSA)的新型合成蛋白纳米颗粒(SPNP),能够通过原本几乎不可渗透的血脑屏障(BBB),将抗癌药物直接递送给恶性脑肿瘤胶质母细胞瘤。

小鼠实验结果表明,合成蛋白纳米颗粒(SPNP)携带STAT3i,成功突破血脑屏障,八只胶质母细胞瘤小鼠中有七只长期存活,并且肿瘤完全消失。这也是第一项证明全身或静脉内输送治疗药物也可以穿越血脑屏障到达脑肿瘤的研究。

早在5年前,该研究的共同通讯作者 Maria Castro 已经开始研究治疗胶质母细胞瘤,她发现了抑制癌细胞发出信号的STAT3等通路,能够欺骗免疫细胞安全通过大脑,然而,她始终没能突破血脑屏障。

后来,在一次学术研讨会上,Maria Castro 和 Joerg Lahann 讨论了这个问题,两个研究团队决定合作研究可以将STAT3抑制剂运送通过血脑屏障的纳米颗粒载体。

研究团队使用了一种称为人类血清白蛋白的蛋白质,该蛋白质是能穿过血脑屏障的少数分子之一,作为其纳米颗粒的结构元件。使用合成分子将这些蛋白质连接起来,然后连接STAT3抑制剂和一种称为iRGD的肽,该肽可用作肿瘤归巢装置。这些元件组成了合成蛋白纳米颗粒(SPNP)。

为了进一步测试合成蛋白纳米颗粒(SPNP)在体内的功效,研究团队使用胶质母细胞瘤小鼠模型进行治疗实验,通过静脉注射 STAT3i SPNP 治疗。

试验结果表明,这些胶质母细胞瘤小鼠模型,未经治疗的中位生存期约为28天,接受空剂SPNP治疗的小鼠,中位生存期为28天不变。

当通过静脉注射 STAT3i SPNP 进行治疗后,胶质母细胞瘤小鼠模型中位生存期增加到了41天,增长率高达45%。

而相同剂量注射游离STAT3i的小鼠模型,中位生存期仅增加5天,这可能是因为静脉注射的全身给药时,siRNA会被快速降解,此外,siRNA也无法穿越有效血脑屏障。

更重要的是,实验的八只小鼠中有七只达到了长期存活,并且肿瘤完全消失,也没有恶性,侵袭性肿瘤细胞存在的迹象。

该研究的通讯作者 Joerg Lahann 表示:这简直是一个奇迹,我们原以为治疗后仍有一定程度的肿瘤存在,没想到肿瘤完全消失了,这是之前从没见到过的。

这是第一项证明全身或静脉内输送治疗药物也可以穿越血脑屏障到达脑肿瘤的研究。 这一发现有望带来治疗胶质母细胞瘤的新临床疗法,为那些原本“不可治疗疾病”带来新的希望。

原始出处:

Jason V Gregory, Padma Kadiyala, Robert Doherty,et al.Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy.Nat Commun. 2020 Nov 10;11(1):5687. doi: 10.1038/s41467-020-19225-7.

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    2021-07-20 liye789132251
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    2021-06-10 珙桐
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    2021-01-04 yinhl1990
  4. [GetPortalCommentsPageByObjectIdResponse(id=1884792, encodeId=973f1884e92af, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 20 21:00:48 CST 2021, time=2021-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970022, encodeId=66b619e00223e, content=<a href='/topic/show?id=ec345834075' target=_blank style='color:#2F92EE;'>#新希望#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58340, encryptionId=ec345834075, topicName=新希望)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25d7319, createdName=珙桐, createdTime=Thu Jun 10 14:00:48 CST 2021, time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1748877, encodeId=1a371e48877ba, content=<a href='/topic/show?id=aed164e34b5' target=_blank style='color:#2F92EE;'>#治癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64734, encryptionId=aed164e34b5, topicName=治癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0d136204823, createdName=yinhl1990, createdTime=Mon Jan 04 07:00:48 CST 2021, time=2021-01-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087821, encodeId=4f26208e821ed, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Wed Aug 11 10:00:48 CST 2021, time=2021-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1262366, encodeId=3c871262366e3, content=<a href='/topic/show?id=ff3c89946de' target=_blank style='color:#2F92EE;'>#血脑屏障#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89946, encryptionId=ff3c89946de, topicName=血脑屏障)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=68b666, createdName=zhangying8788, createdTime=Mon Nov 16 07:00:48 CST 2020, time=2020-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1323418, encodeId=9ee4132341865, content=<a href='/topic/show?id=d8d5e7476de' target=_blank style='color:#2F92EE;'>#纳米颗粒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77476, encryptionId=d8d5e7476de, topicName=纳米颗粒)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/WQ1WyMBGic8d2fKdCe6Cm3vaRh4X8YnlumYndC46iagNCBl9Df8RtoCaQchnFtZldHUctGJjsgsyutUlu8vPq6yQ/132, createdBy=97862500016, createdName=ms3117646317107274, createdTime=Mon Nov 16 07:00:48 CST 2020, time=2020-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1418045, encodeId=b8c9141804524, content=<a href='/topic/show?id=6ba485016cd' target=_blank style='color:#2F92EE;'>#脑肿瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85016, encryptionId=6ba485016cd, topicName=脑肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=76f03326658, createdName=839640779, createdTime=Mon Nov 16 07:00:48 CST 2020, time=2020-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=899201, encodeId=971789920133, content=能不能尽快对人体进行临床实验?, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5af5325692, createdName=金黎明, createdTime=Sat Nov 14 21:30:22 CST 2020, time=2020-11-14, status=1, ipAttribution=)]
    2021-08-11 liuli5079
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    2020-11-14 金黎明

    能不能尽快对人体进行临床实验?

    0

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