尽管人们在检测、诊断和治疗脑部肿瘤中取得很大进步，但是脑癌患者存活率一直比较低，部分上是因为脑癌的高水平治疗抗性。根据2012年2月17日发表在生物医学中心(BioMed Central)旗下开放存取的Journal of Nanobiotechnology 期刊上的一篇新研究论文，研究人员使用仙台病毒(Sendai Virus，一种乙型副流感病毒)转运量子点(Quantum Dots, Qdots)到脑癌细胞中，而且将量子点特异性地结合到经常在肿瘤中活性上调和过量表达的表皮生长因子受体(epidermal growth factor receptor, EGFR)。通过分子标记癌细胞，这种纳米颗粒就能够被用来辅助脑癌诊断。
该研究所用的量子点是微小的荧光颗粒，比病毒还要小，比细胞要小1000多倍，能够与诸如抗体之类的生物分子偶联在一起。一旦偶联在一起，量子点发出的荧光就很容易让科学家找出哪些细胞含有抗体识别的蛋白，以及细胞中这种蛋白位于何处。然而，一直以来存在这种问题：进入细胞的量子点结成块，或者被胞内体(endosome)包被而作为废弃物分泌到细胞外。
来自美国纽约市立学院(City College of New York)的研究人员通过将量子点包被在仙台病毒的脂质和蛋白外壳之中而战胜这种难题。Maribel Vazquez教授解释道，“尽管细胞有复杂的防御机制保护自己免受攻击，但是病毒已经进化出欺骗细胞放行进入细胞内的方法。我们能够利用这些机制将失活的小鼠副流感病毒(parainfluenza virus)与含有量子点的脂质体融合在一起，其中量子点附着到抗EGFR的一种抗体上。因此，一旦进入细胞内部，量子点-抗体复合体能够结合到EGFR上，而且结合的复合体数量能够通过测量量子点荧光而进行监控。”
这项研究是利用EGFR作为癌症的一种标记物来开展研究的，但是量子点能够附着到任何抗体上。抗体-量子点复合体将允许科学家快速鉴定不同的癌症类型，确定潜在性的化疗耐受性以及开展一种更加个人化的治疗方案。(生物谷：towersimper编译)
doi:10.1186/1477-3155-10-9
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Sendai Virus-based Liposomes Enable Targeted Cytosolic Delivery of Nanoparticles in Brain Tumor-Derived Cells
Veronica Dudu, Veronica Rotari and Maribel Vazquez
Background Nanotechnology-based bioassays that detect the presence and/or absence of a combination of cell markers are increasingly used to identify stem or progenitor cells, assess cell heterogeneity, and evaluate tumor malignancy and/or chemoresistance. Delivery methods that enable nanoparticles to rapidly detect emerging, intracellular markers within cell clusters of biopsies will greatly aid in tumor characterization, analysis of functional state and development of treatment regimens.
Results Experiments utilized the Sendai virus to achieve in vitro, cytosolic delivery of Quantum Dots (Qdots) in cells cultured from Human brain tumors. Using fluorescence microscopy and Transmission Electron Microscopy (TEM), in vitro experiments illustrate that our virus-based liposomes (VBL) decreased the amount of non-specifically endocytosed nanoparticles by 50% in the Human glioblastoma (GBM) and medulloblastoma (MB) samples studied. Significantly, VBL delivery also facilitated targeted binding of Qdots to cytosolic Epidermal Growth Factor Receptor (EGFR) within cultured cells, focal to the early detection and characterization of malignant brain tumors.
Conclusions These findings are the first to utilize the Sendai virus to achieve cytosolic, targeted intracellular binding of Qdots within Human brain tumor cells. The results are significant to the continued applicability of nanoparticles used for the molecular labeling of cancer cells to determine tumor heterogeneity, grade, and chemotherapeutic resistivity.
