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儿童肿瘤药物开发存短板 新型载药系统有望补位

编辑:全球肿瘤医生网2016-08-21 11:20

 

2015年4月14日讯 /生物谷BIOON/ --随着人们对肿瘤发生机制认识的深入,科学家们相继开发出了越来越多的特效肿瘤疗法。然而,这些疗法通常都是基于成人临床试验得到的。这也意味着目前在儿童癌症研究中仍然存在着很大的短板。事实上,根据美国费城儿童医院(CHOP)的研究人员介绍,目前临床上仍然缺少专门针对儿童的抗肿瘤药物。许多治疗方案都是沿用着30-40年前的药物疗法。

有鉴于此,近些年来,CHOP的研究人员纷纷投入到儿童肿瘤药物研发中。最近他们发现了一种新型生物可降解纳米颗粒SN38能够靶向运输抗癌药物用于治疗神经母细胞瘤。这种肿瘤类型常见于儿童群体中,是最为恶性的肿瘤类型之一。

负责进行这一实验的研究人员介绍说,这一纳米载药系统主要应用了一种名为EPR效应(通透性增强与滞留效应)的原理。肿瘤部位细胞由于遗传物质的改变导致该部位的血管无法正常生长并出现局部的不完整部分和"漏洞",这些"漏洞"能够允许特定尺寸范围的颗粒运输并富集在该部位。研究人员基于这一原理开发出了这种名为SN38的纳米颗粒。而相关动物实验表明,用SN38纳米颗粒运输的伊立替康对小鼠肿瘤的治疗效果是单用伊立替康的100倍。同时,在给药后的72小时内,小鼠均未出现明显的毒副作用。这也意味着这种载药系统能够有效降低药物的毒副作用。相对于成人患者,儿童的身体更为虚弱,这也是目前制约儿童肿瘤药物开发的一个重要问题。

来自CHOP的研究人员希望未来这种疗法能够进入到临床帮助更多的儿童肿瘤患者。(生物谷Bioon.com)

详细英文报道:

At the Children's Hospital of Philadelphia (CHOP), researchers are looking toward biodegradable nanoparticles capable of delivering cancer drugs to neuroblastoma without harming surrounding tissue.

The nanoparticles take advantage of what scientists call the "EPR effect"--enhanced permeability and retention--to target the drugs. This weakness in tumors causes blood vessels to form incorrectly and become more leaky and disorganized, the researchers said. Thus, they designed the nanoparticles to bypass what can be identified as healthy tissue by its organized blood vessel structure and instead take aim at the tangled mess at the tumor site.

The scientists delivered the nanoparticle-encapsulated drug, called SN38, to mice. They found that the mice with the new drug had 100 times the amounts of the active treatment delivered to the tumor than mice with the traditional cancer drug irinotecan. The treatment persisted 72 hours with no evidence of toxicity, according to a hospital report.

"We carefully adjust the size of the nanoparticles to find a 'sweet spot': small enough to penetrate a tumor, and large enough to carry a therapeutic payload," researcher Michael Chorny said in a statement. "We can also adjust their composition to keep the active molecule entrapped in a polymer until nanoparticles reach the targeted tumor, and customize the timing of the polymer's breakdown to allow controlled release of SN38 over a time scale that provides the best therapeutic effects."

The rate of improvement in treatments for childhood cancers has lagged behind that in adult cancers, with neuroblastoma in particular, according to the hospital.

"In pediatric oncology, we have largely relied on drugs developed 30 to 40 years ago," CHOP researcher Garrett Brodeur said. "While these have greatly improved overall cure rates over that period from 20 percent to 80 percent, we still need better drugs and more targeted approaches for the most stubborn childhood cancers, including high-risk forms of neuroblastoma."

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