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Cancer Research:运用纳米粒子运送基因治疗卵巢癌

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来源: 标签:基因治疗卵巢癌粒子 2009-09-03 11:13:21
  美国研究人员30日报告说,他们利用纳米粒子作为载体,把编码某种毒素的基因输入患有卵巢癌的实验鼠体内,很好地抑制了癌细胞的生长。

  美国研究人员30日报告说,他们利用纳米粒子作为载体,把编码某种毒素的基因输入患有卵巢癌的实验鼠体内,很好地抑制了癌细胞的生长。

  来自麻省理工学院等机构的研究人员在新一期《癌症研究》杂志上报告说,在这一新的研究成果基础上,他们有望开发出新的卵巢癌治疗方法。进一步研究后,预计一至两年内就可以对新治疗方法进行人体临床试验。

  研究人员用纳米粒子输送的是一种“杀手”基因,因为它负责编码产生白喉毒素。这种毒素可以扰乱细胞,使细胞无法正常生产蛋白质,从而失去正常功能。不过,研究人员解释说,他们对这种基因进行了基因工程处理,使它只在卵巢癌的癌细胞中过度表达,抑制癌细胞生长,但在其他类型的细胞中会保持“沉默”,因此整个过程不会对实验鼠造成毒副作用。

  相比之下,目前卵巢癌患者接受手术后,还需持续进行化疗,会产生一定的毒副作用。另外,卵巢癌患者术后还经常面临复发风险,对于复发以及晚期的卵巢癌,目前缺乏较好的治疗方案。

  接下来,研究人员还将尝试利用这一纳米粒子基因递送系统,对其他类型癌症进行治疗。(生物谷Bioon.com)

  推荐原始出处:

  Cancer Research 69, 6184, August 1, 2009. doi: 10.1158/0008-5472.CAN-09-0061

  Nanoparticle-Delivered Suicide Gene Therapy Effectively Reduces Ovarian Tumor Burden in Mice

  Yu-Hung Huang1, Gregory T. Zugates2, Weidan Peng1, David Holtz1, Charles Dunton1, Jordan J. Green2, Naushad Hossain2, Michael R. Chernick1, Robert F. Padera, Jr.4, Robert Langer2,3, Daniel G. Anderson2 and Janet A. Sawicki1,5,6

  1 Lankenau Institute for Medical Research, Wynnewood, Pennsylvania; 2 David H. Koch Institute for Integrative Cancer Research and 3 Chemical Engineering Department, Massachusetts Institute of Technology, Cambridge, Massachusetts; 4 Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; 5 Department of Dermatology and Cutaneous Biology and 6 Kimmel Cancer Center, Jefferson Medical School, Thomas Jefferson University, Philadelphia, Pennsylvania

  There is currently no effective therapy for patients with advanced ovarian cancer. To address the need for a more effective treatment for this deadly disease, we conducted preclinical tests in ovarian tumor–bearing mice to evaluate the therapeutic efficacy of using a cationic biodegradable poly(β-amino ester) polymer as a vector for nanoparticulate delivery of DNA encoding a diphtheria toxin suicide protein (DT-A). The promoter sequences of two genes that are highly active in ovarian tumor cells, MSLN and HE4, were used to target DT-A expression to tumor cells. Administration of DT-A nanoparticles directly to s.c. xenograft tumors and to the peritoneal cavity of mice bearing primary and metastatic ovarian tumors resulted in a significant reduction in tumor mass and a prolonged life span compared to control mice. Minimal nonspecific tissue and blood chemistry toxicity was observed following extended treatment with nanoparticles. DT-A nanoparticle therapy suppressed tumor growth more effectively than treatment with clinically relevant doses of cisplatin and paclitaxel. Our findings suggest that i.p. administration of polymeric nanoparticles to deliver DT-A encoding DNA, combined with transcriptional regulation to target gene expression to ovarian tumor cells, holds promise as an effective therapy for advanced-stage ovarian cancer.

 

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