奈米微粒蛋白質 可殺死癌細胞【台灣醒報╱記者李昀澔╱台北報導】 2014.01.08 09:33 pm 帶有抗癌蛋白質的奈米微粒，可殺死癌細胞，遏止腫瘤擴散。美國康乃爾大學團隊發表於《美國國家科學院刊》的研究，把能殺死癌細胞的蛋白質貼附於奈米微粒表面，再將奈米微粒注入血液，結果發現能有效殺死轉移中的癌細胞。該實驗目前仍在體外模擬試驗階段，未來可望成為臨床上在手術及放射治療前的前置作業。一般定義癌症進入末期，多指癌細胞已透過血液轉移至身體其他部位，9成癌症病患都因癌細胞擴散致死。康乃爾大學團隊將一種稱為「腫瘤壞死因子相關細胞凋亡誘導配體」（簡稱TRAIL）的蛋白質貼附在奈米微粒表面，再把奈米微粒注入血液，發現奈米微粒會吸附在一種稱為「自然殺手」細胞的白血球表面，等於幫自然殺手添加裝備，成為殺死癌細胞能力更強的「超」自然殺手。
【自然殺手細胞升級】TRAIL是人體免疫系統自然產生的一種抗癌蛋白質，能引發癌細胞內部產生類似「自殺」的反應；當癌細胞脫離腫瘤主體的位置，順著血流移動的時候，可能會與帶有TRAIL奈米微粒的白血球「相碰」，因而促進癌細胞死亡，達到阻止腫瘤擴散的目的。康乃爾大學教授麥可金恩表示，研究人員在模擬人類及動物的大腸癌及攝護腺癌腫瘤組織的實驗中，將帶有TRAIL的奈米微粒注入血流後2小時觀察，都發現癌細胞數目減少，甚至大塊腫瘤組織已有瓦解現象產生。金恩認為，該療法可作為現行手術或放療前的前置工作，清除在血液中「游離」的癌細胞，以確保手術清除腫瘤的效果。
【奈米微粒抗癌新趨勢】研究團隊目前已證實，注入奈米微粒僅會增加自然殺手細胞的抗癌能力，不會改變其他免疫系統原有的功能，也就是包括其他血球及血管內壁等正常細胞不會因此受到攻擊；但由於目前無從得知實際打入生物體內的效果及副作用，因此在進入臨床人體試驗前，必須選擇比老鼠更大型、更接近人類的哺乳動物進行實驗。運用奈米微粒作為藥物「載體」已是癌症治療研究趨勢，北卡大學教堂山分校與北卡州立大學團隊合作，日前發表於德國期刊《進階功能性材料》的研究，便將TRAIL與另一種抗癌藥物「DOX」貼附在奈米微粒的表面，同樣具備殺死癌細胞的功效。【2014/01/08 台灣醒報】
Nanoparticles catch cancer in pincer movement 13 January 2014 Researchers have developed a technique for creating nanoparticles that carry two different cancer-killing drugs into the body and deliver them to separate parts of the cancer cell. The technique was developed by researchers at North Carolina State University and the University of North Carolina at Chapel Hill.'In testing on laboratory mice, our technique resulted in significant improvement in breast cancer tumour reduction as compared to conventional treatment techniques,' said Dr Zhen Gu, senior author of a paper on the research and an assistant professor in the joint biomedical engineering program at NC State and UNC-Chapel Hill. 'Cancer cells can develop resistance to chemotherapy drugs, but are less likely to develop resistance when multiple drugs are delivered simultaneously,' Gu said in a statement. 'However, different drugs target different parts of the cancer cell. For example, the protein drug TRAIL is most effective against the cell membrane, while doxorubicin (Dox) is most effective when delivered to the nucleus. We've come up with a sequential and site-specific delivery technique that first delivers TRAIL to cancer cell membranes and then penetrates the membrane to deliver Dox to the nucleus.' Gu's research team developed nanoparticles with an outer shell made of hyaluronic acid (HA) woven together with TRAIL. The HA is said to interact with receptors on cancer cell membranes, which 'grab' the nanoparticle. Enzymes in the cancer cell environment break down the HA, releasing TRAIL onto the cell membrane and ultimately triggering cell death. When the HA shell breaks down, it also reveals the core of the nanoparticle, which is made of Dox that is embedded with peptides that allow the core to penetrate into the cancer cell. The cancer cell encases the core in a protective bubble - an endosome - but the peptides on the core cause the endosome to begin breaking apart. This spills the Dox into the cell where it can penetrate the nucleus and trigger cell death.'We designed this drug delivery vehicle using a 'programmed' strategy,' said Tianyue Jiang, a lead author in Dr. Gu's lab.'Different drugs can be released at the right time in their right places,' said Dr Ran Mo, a postdoctoral researcher in Gu's lab and the other lead author.'This research is our first proof of concept, and we will continue to optimize the technique to make it even more efficient,' Gu says. 'The early results are very promising, and we think this could be scaled up for large-scale manufacturing.'
The paper, 'Gel–Liposome-Mediated Co-Delivery of Anticancer Membrane-Associated Proteins and Small-Molecule Drugs for Enhanced Therapeutic Efficacy,' is published online in Advanced Functional Materials.
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