盡管人們在檢測,、診斷和治療腦部腫瘤中取得很大進步，但是腦癌患者存活率一直比較低,，部分上是因為腦癌的高水平治療抗性,。根據(jù)2012年2月17日發(fā)表在生物醫(yī)學中心(BioMed Central)旗下開放存取的Journal of Nanobiotechnology 期刊上的一篇新研究論文,，研究人員使用仙臺病毒(Sendai Virus，一種乙型副流感病毒)轉(zhuǎn)運量子點(Quantum Dots, Qdots)到腦癌細胞中,，而且將量子點特異性地結(jié)合到經(jīng)常在腫瘤中活性上調(diào)和過量表達的表皮生長因子受體(epidermal growth factor receptor, EGFR),。通過分子標記癌細胞，這種納米顆粒就能夠被用來輔助腦癌診斷,。
該研究所用的量子點是微小的熒光顆粒,，比病毒還要小，比細胞要小1000多倍,，能夠與諸如抗體之類的生物分子偶聯(lián)在一起,。一旦偶聯(lián)在一起，量子點發(fā)出的熒光就很容易讓科學家找出哪些細胞含有抗體識別的蛋白,，以及細胞中這種蛋白位于何處,。然而，一直以來存在這種問題：進入細胞的量子點結(jié)成塊,，或者被胞內(nèi)體(endosome)包被而作為廢棄物分泌到細胞外,。
來自美國紐約市立學院(City College of New York)的研究人員通過將量子點包被在仙臺病毒的脂質(zhì)和蛋白外殼之中而戰(zhàn)勝這種難題。Maribel Vazquez教授解釋道,，“盡管細胞有復雜的防御機制保護自己免受攻擊,，但是病毒已經(jīng)進化出欺騙細胞放行進入細胞內(nèi)的方法。我們能夠利用這些機制將失活的小鼠副流感病毒(parainfluenza virus)與含有量子點的脂質(zhì)體融合在一起,，其中量子點附著到抗EGFR的一種抗體上,。因此，一旦進入細胞內(nèi)部,，量子點-抗體復合體能夠結(jié)合到EGFR上,，而且結(jié)合的復合體數(shù)量能夠通過測量量子點熒光而進行監(jiān)控。”
這項研究是利用EGFR作為癌癥的一種標記物來開展研究的,，但是量子點能夠附著到任何抗體上,。抗體-量子點復合體將允許科學家快速鑒定不同的癌癥類型,，確定潛在性的化療耐受性以及開展一種更加個人化的治療方案,。(生物谷：towersimper編譯)
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.
