PLoS：新型治疗肠癌放疗试剂进入细胞内起效

xielirong

Inside job: new radioactive agents for colon cancer work inside cells
Johns Hopkins scientists have developed a potentially novel way to fight colorectal cancer using tiny molecules to deliver potent barrages of radiation inside cancer cells, unlike current treatments that bind to the surface of cells and attack from the outside and cause unwanted side effects.

In laboratory studies with normal and cancer cells, the new radiation delivery system proved able to specifically target colon cancer cells, and what’s left over is likely to be easily filtered out by the kidneys because the delivery system’s molecules are so small.

As reported online in PLoS One on October 3, Hopkins colorectal cancer specialists John Abraham, Ph.D., and Stephen Meltzer, M.D. -working with the notion that small molecules generally make better treatment packages-designed small bits of protein only 10 amino acids long as the foundation for their drugs. By contrast, antibodies used to deliver radiation or chemicals can be over one thousand amino acids long.

The team attached radioactive phosphorous, P32, as a test of how well their peptides worked and “to our surprise, our first tests showed that cells were ingesting these molecules, thus transferring the radiation inside and killing them by breaking up their DNA and proteins,” Abraham says.

While cautioning that the new radiation delivery system is still far from ready for use in people, Abraham notes that P32 gives off high energy that can penetrate through 5 millimeters of human tissue, making it a good candidate to tackle colon cancer since colon cancer cells can often form large, thick tumors into which drugs may not penetrate very well. In addition, P32-labeled peptides may serve another valuable use: to find small metastases or recurrences of colon tumors while they are still small enough to treat. Images of the body can be taken of the labeled peptides as they bind, revealing where stray tumor cells may be nesting.

Abraham, Meltzer and their team then designed and tested a variety of P32-peptides on 18 normal and cancerous human cell samples. The most potent peptide, MA5, could bind to adenocarcinoma cells, which make up 95 percent of all colon cancers, 150 times more strongly than other cell types and be transferred inside cells within 2 hours.

Source: Johns Hopkins Medical Institutions

译文：


Johns Hopkins大学的科学家最近发明了一种治疗直肠结肠癌的新方法，他们利用小型分子将放射试剂输送到癌细胞内，而不像目前的方法一样是结合到细胞表面来从外部攻击癌细胞，这会造成有害副作用。

在实验室中针对正常细胞和癌细胞进行的实验中，新的放射试剂输送系统被证明能特定攻击肠癌细胞，而剩余的物质能很容易的被肾脏滤出，因为输送系统的分子非常小。

在10月3日的在线版PLoS上，Hopkins的肠癌专家John Abraham和Stephen Meltzer博士利用小分子能获得更好的疗效的想法，设计了只有10个氨基酸长度的小型蛋白质，并将其作为他们药物的基础。与此相比，携带放疗或化疗试剂的抗体能超过1000个氨基酸长度。

小组在分子上结合了放射性磷P32，以测试他们的多肽能有多好的效果，结果Abraham表示：“令人惊讶的是，第一项测试就显示细胞能吞入这些分子，从而将放疗剂送入细胞内，并通过破坏DNA和蛋白质来杀死癌细胞。”

科学家同时警告这种新型放疗剂输送系统还不能用于人类，但Abraham注意到P32能发出极高能量，并穿透5毫米厚的人体组织，这意味着它是治疗肠癌的很好试剂，因为肠癌常常会形成大而厚的组织，药物无法很好穿透。除此之外P32结合的多肽还有一个用处：在肿瘤还很小时发现肠癌的转移和复发。这些多肽能反应出漂移的癌细胞所处位置。

随后Abraham、Meltzer以及他们的小组设计了多种P32-多肽，并在18份正常或癌变人类细胞样本中进行了测试。其中最有效的多肽MA5能和腺癌细胞结合，腺癌构成了肠癌的95%，这比其它细胞类型强150倍，并能在2小时内进入到细胞内。