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纳米技术平台为治疗胰腺癌提供了希望

本文作者:最新it技术网 更新时间:2019-09-01 10:06:29

  加州大学洛杉矶分校的加州纳米系统研究所和琼森综合癌症中心的纳米技术专家们合作创建了一种新的治疗方法,解决使用化疗方法治疗胰腺癌中存在的一些问题。

  这项研究的成果发表在《ACS Nano》期刊网络版上。科学家们阐述了这项成功的试验,在一个特别设计的介孔二氧化硅纳米粒子中(看起来像一个玻璃泡)混入了两种药物。药物共同作用成功地缩小了小鼠身上的人类胰腺肿瘤,但使用剂量只是目前治疗方法的十二分之一。低剂量能够降低治疗费用并减少目前治疗方法的副作用。

  这项研究由琼森癌症中心的医学助理教授Huan Meng博士,和著名医学教授Andre Nel博士领导完成。

  胰腺癌是一个恶性程度很高的疾病,5年生存率只有5%,早期的确诊率不高,病程短病情发展快。很多人在确诊的时候就已经错过了最佳治疗期,化疗是唯一可行的治疗选择。最常用的胰腺癌化疗药物是吉西他滨,但其作用有限。

  最新研究发现,吉西他滨与另一种叫做紫杉醇的药物结合可以提高整体治疗效果。目前的治疗方法,分别服用紫杉醇新制剂Abraxane和吉他西滨,能够起到一定作用,但是由于药物在人体内停留时间不同,药物协同作用效果就没有体现出现。

  “硅纳米技术的优势就是将吉他西滨和紫杉醇以精确的比例放入一个特殊的脂质纳米颗粒中,使它们同时被送到癌细胞部位,发挥彼此的协同作用,通过单一的药物载体达到最好的治疗效果。”Meng说。“这种方法能够减少药物剂量,还能发挥组合优势。”

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  科学家们创造了硅纳米颗粒之后,将它们置于血清中,然后注射进患有胰腺肿瘤的小鼠体内。其他患有胰腺肿瘤的小鼠被注射了生理盐水(没有作用的安慰剂),吉西他滨(标准治疗方法)以及吉西他滨和紫杉醇新制剂Abraxane(2013年,FDA宣布批准Abraxane——白蛋白结合型紫杉醇联合吉西他滨用于转移性胰腺癌的一线治疗)。

  接受纳米粒子中两种药物治疗的小鼠,胰腺肿瘤比对照组明显缩小。

  类似的对比已经在小鼠模型中进行了,将人类肿瘤手术植入小鼠的腹部,是为了方便地模拟胰腺肿瘤的起源点并更好地提供人类肿瘤的平行研究。在这些实验室,接受硅纳米颗粒治疗的小鼠,它们的肿瘤比对照组的明显缩小。同时,在这些小鼠身上没有发生癌症转移或蔓延到附近器官的现象。

  “不仅仅是一个癌症原理循证研究的实验室,我们利用定制纳米载体专门攻克胰腺癌。Nel说,他也是加利福尼亚纳米系统研究所的副主任。“在我们的平台上,药物要真正发挥协同性,因为我们会控制药物的混合量,让纳米颗粒中药物混合的比例达到最佳,以达到最棒的治疗效果。”

  Meng说硅纳米载体还在提纯以便于人类使用。研究人员希望能够在未来五年内,对这个治疗平台进行临床试验。

  Nanotechnology platform shows promise for treating pancreatic cancer

  Scientists at UCLA’s California NanoSystems Institute and Jonsson

  Comprehensive Cancer Center have combined their nanotechnology expertise to

  create a new treatment that may solve some of the problems of using chemotherapy to treat pancreatic cancer.

  The study, published online in the journal ACS Nano, describes successful

  experiments to combine two drugs within a specially designed mesoporous silica nanoparticle

  that looks like a glass bubble. The drugs work together to shrink human pancreas

  tumors in mice as successfully as the current standard treatment, but at one twelfth the dosage.

  This lower dosage could reduce both the cost of treatment and the side effects that people suffer from the current method.

  The study was led by Dr. Huan Meng, assistant adjunct professor of medicine,

  and Dr. Andre Nel, distinguished professor of medicine, both at the Jonsson Cancer Center.

  Pancreatic cancer, a devastating disease with a five- year survival rate of 5 percent, is difficult to detect early and symptoms do not usually appear

  until the disease is advanced. As a result, many people are not diagnosed until

  their tumors are beyond the effective limits of surgery, leaving chemotherapy as

  the only viable treatment option. The chemotherapy drug most often used for pancreas cancer is gemcitabine, but its impact is often limited.

  Recent research has found that combining gemcitabine with another drug

  called paclitaxel can improve the overall treatment effect. In the current method, Abraxane— a nano complex containing paclitaxel— and gemcitabine are given separately, which works to a degree, but because the drugs

  may stay in the body for different lengths of time, the combined beneficial effect is not fully synchronized.

  'The beauty of the silica nanoparticle technology is that gemcitabine and paclitaxel are placed together in one special lipid-coated nanoparticle at the exact ratio that makes them synergistic with one another when co- delivered at the cancer site, giving us the best possible outcome by using a single drug carrier,' Meng said. 'This enables us to reduce the dose and maintain the combinatorial effect.'

  After the scientists constructed the silica nanoparticles, they suspended them in blood serum and injected them into mice

  that had human pancreas tumors growing under their skin. Other mice with tumors

  were given injections of saline solution (a placebo with no effect), gemcitabine (the treatment standard), and gemcitabine and Abraxane (an FDA-approved combination shown to improve pancreas cancer survival in humans).

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  In the mice that received the two drugs inside the nanoparticle, pancreas tumors shrank dramatically compared with those in the other mice.

  Similar comparisons were made with mouse models, in which the human tumors were surgically

  implanted into the mice’s abdomens in order to more closely emulate the natural point of origin of pancreatic

  tumors and provide a better parallel to the tumors in humans. In these experiments, the tumors in the mice

  receiving silica nanoparticles shrank more than the comparative controls. Also, metastasis, or tumor spread, to nearby organs was eradicated in these mice.

  'Instead of just a laboratory proof-of- principle study of any cancer, we specifically attacked pancreatic cancer with a custom- designed nanocarrier,' said Nel, who is also associate director for research of the California NanoSystems Institute. 'In our platform,

  the drugs are truly synergistic because we have control over drug mixing, allowing us to incorporate optimal ratios in our particles,

  making the relevance of our models very high and our results very strong.'

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  Meng said the silica nanocarrier must still be refined for use in humans.

  The researchers hope to test the platform in human clinical trials within the next five years.

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