Sci Rep:特异性杀伤肿瘤细胞的纳米技术

Scientific Reports杂志上发表Dalhousie医学院的研究人员的一项新研究工作,研究人员开发了一种运送化疗药物的新方式。这种利用纳米科技的新型药物运送系统仅仅在肿瘤细胞释放药物,从而保护健康细胞不受伤害。

Naga Puvvada博士发明了药物运送系统。他与DMNB的Keith Brunt博士,及美国和印度的研究人员们一起合作,开发了这种新系统。研究团队设计了一种纳米颗粒,这种颗粒可以增加运送到肿瘤细胞的化疗药物的量,而且仅仅在肿瘤细胞内释放化疗药物。这样就对健康组织的影响减少到了最低。

肿瘤细胞产生的高酸性水平,才可以激活纳米颗粒,从而使其进入到肿瘤细胞,释放药物。当纳米颗粒释放药物时,它的颜色会改变,即光转换。这种光转换就可以帮助研究人员了解,多少化疗药物得到了释放,及辨别出存在的肿瘤。

"我们设计的独到之处就是,荧光光转换潜在的临床转化可能性,因为它有助于检测到化疗药物的释放量。"Puvvada博士说。"在这项技术用于临床之前,我们仍将有许多工作要做,因为目前荧光还不能够被MRIs 或 CTs检测到。这是我们下一步的研究工作。"

尽管这项研究是在人类乳腺癌细胞上开展的,但这项技术有潜力运用到任何一种实体瘤上。

"尽管这种新的药物运送系统还在早期阶段,但是它很有希望成为患者个体化治疗的一个方法。"药理系助理教授Brunt博士说。"这种靶向性好,且可以检测药物释放量的治疗方法,有潜力提高实体瘤患者的生活质量,他们的总体效果指日可待。"

原文链接:

Novel ZnO hollow-nanocarriers containingpaclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

原文摘要:

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.

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