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黄蜂毒液杀死癌细胞的策略

作者:admin 发表于:2014-08-08 点击:620  保护视力色:
尽管目前正在开发各种化合物对抗癌症,但它们都具有严重的副作用。科学家们设计了一种基于肽的新疗法,利用黄蜂毒液中的多肽,作为预防乳腺癌的潜在新方法。


科学探索

 
黄蜂毒液杀死癌细胞的策略
 

  尽管目前正在开发各种化合物对抗癌症,但它们都具有严重的副作用。此外,肿瘤能够对这些化合物产生耐药。

  为了抵消上述两个缺点,科学家们设计了一种基于肽的新疗法,利用黄蜂毒液中的多肽,作为预防乳腺癌的潜在新方法。

  这种肽具有在细胞质膜形成孔的能力,并穿透进入癌细胞,或诱导癌细胞坏死或触发凋亡,最后导致癌细胞死亡。

  然而,这种强大的“自然武器”目前还不能用于治疗,这是由于它的高毒性和缺乏细胞特异性,它不仅会损害肿瘤细胞,也将影响患者的健康细胞。因此,研究人员设计一种手段,以一个特定的和可控制的方式输送肽到肿瘤,并使其在肿瘤细胞中堆积。

  该系统由装载两个“组件”的载体聚合物组成:能绑定到肿瘤细胞受体的肽和黄蜂毒液的毒性肽。体外实验表明,黄蜂毒液的毒性肽被充分地递送分布在肿瘤细胞内,并导致其死亡,而正常细胞如红细胞不受影响。

  研究结果已发表在JouRNAl of Controlled Release杂志上,目前研究仍然处于早期阶段,接下来的步骤是通过小鼠体内试验来测试其功效。(来源:生物帮)


  原文摘要:

Delivering wasp venom for cancer therapy

Miguel Moreno, Esther Zurita, Ernest Giralt

  Cytolytic peptides with potential therapeutic properties have appeared during the last three decades. However, the use of these natural weapons is relatively narrow due to their non-specific cytolytic activity as well as their rapid degradation and excretion when injected in blood. In order to rescue the use of these lytic peptides, we have designed pro-cytotoxic systems based on cytotoxic peptides conjugated to poly(l-glutamic acid) PGA polymer through specific cleavage sequences that are sensitive over-expressed tumor proteases, such as the metalloproteinase-2 (MMP-2) or cathepsin B. The potent cytotoxic peptide tested here, Mitoparan, is inactive when conjugated to the polymer and then become active again once released through the tumor proteases. Furthermore, this pro-cytotoxic system was decorated by a particular targeting peptide which binds to HER2 receptors over-expressed in some types of breast tumor cells, thereby increasing the selective release of cytolytic peptides inside tumor cell with exquisite spatiotemporal control. In this way, the system would improve the maximum tolerated dose and the pharmacokinetic parameters of cytotoxic peptides in vivo.