美國研究人員30日報(bào)告說,他們利用納米粒子作為載體,,把編碼某種毒素的基因輸入患有卵巢癌的實(shí)驗(yàn)鼠體內(nèi),,很好地抑制了癌細(xì)胞的生長。
來自麻省理工學(xué)院等機(jī)構(gòu)的研究人員在新一期《癌癥研究》雜志上報(bào)告說,,在這一新的研究成果基礎(chǔ)上,,他們有望開發(fā)出新的卵巢癌治療方法。進(jìn)一步研究后,,預(yù)計(jì)一至兩年內(nèi)就可以對新治療方法進(jìn)行人體臨床試驗(yàn),。
研究人員用納米粒子輸送的是一種“殺手”基因,因?yàn)樗?fù)責(zé)編碼產(chǎn)生白喉毒素,。這種毒素可以擾亂細(xì)胞,,使細(xì)胞無法正常生產(chǎn)蛋白質(zhì),從而失去正常功能,。不過,,研究人員解釋說,他們對這種基因進(jìn)行了基因工程處理,,使它只在卵巢癌的癌細(xì)胞中過度表達(dá),,抑制癌細(xì)胞生長,但在其他類型的細(xì)胞中會(huì)保持“沉默”,,因此整個(gè)過程不會(huì)對實(shí)驗(yàn)鼠造成毒副作用,。
相比之下,目前卵巢癌患者接受手術(shù)后,,還需持續(xù)進(jìn)行化療,,會(huì)產(chǎn)生一定的毒副作用。另外,,卵巢癌患者術(shù)后還經(jīng)常面臨復(fù)發(fā)風(fēng)險(xiǎn),,對于復(fù)發(fā)以及晚期的卵巢癌,目前缺乏較好的治療方案。
接下來,,研究人員還將嘗試?yán)眠@一納米粒子基因遞送系統(tǒng),,對其他類型癌癥進(jìn)行治療。(生物谷Bioon.com)
生物谷推薦原始出處:
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.