粘性纳米颗粒，精确地向目标位置输送药物，然后停留在目标位，在对抗卵巢癌和子宫癌方面发挥了至关重要的作用。
耶鲁大学的研究团队发现，用充满有效化疗药物的，具有生物黏附性的纳米颗粒进行治疗，比妇科肿瘤的常规治疗方法更加有效，而且毒性较低。耶鲁大学工程与应用科学学院的马克 萨尔茨曼教授和耶鲁大学医学院的阿里桑德罗 桑廷教授共同领导了这项研究，研究成果发表在9月19日的美国国家科学院院刊上。
纳米颗粒中充入的药物是埃坡霉素B（EB），将纳米颗粒注入腹膜间隙，腹腔中的液体。EB已经被用于临床试验，用于靶向那些对常规化疗制剂具有抗药性的肿瘤细胞。该药物在这些临床试验中被证明是有效的，但是药物的高毒性引起了严重的副作用，从而阻止的该药物的进一步使用。
耶鲁癌症中心研究人员的处理方法，将药物充入纳米颗粒中，显著降低了药物毒性，并在肿瘤部位逐步释放高浓度的药物。科学家们意识到，传统纳米颗粒的问题是，它们从目标区域的离开速度太快，而且由于体积小，产生的作用不大。
“我们面临的挑战是要找到一种使用药物的方法，如果你能让它长时间地停留在正确的位置上，那么这个方法就是有效的，” 耶鲁大学化学和生物医学工程戈伊苏埃塔基金会教授萨尔茨曼说。
为此，耶鲁团队开发了覆盖醛基的纳米粒子，当它们被注入腹膜后，可以粘附在腹腔的间皮细胞上。将人类肿瘤移植到老鼠的腹部分区，肿瘤生长过程中，在老鼠身上进行测试，生物黏附纳米颗粒能够在指定位置停留至少24小时。非黏附纳米颗粒注射到对照组小鼠身上，五分钟后开始离开腹腔。接受生物黏附纳米颗粒治疗的老鼠，有60%存活了4个月，比起对照组有明显的改善，对照组只有10%或更少的老鼠能存活4个月。
桑廷说，通过定位化地传输药物，他们既降低了药物毒性，也增加了其有效性。这种治疗方法特别有利于卵巢和子宫癌的晚期患者，因为这部分人的癌细胞已经扩散到腹膜区域所以对他们的治疗是非常困难的，他说。
“他们已经接受了手术和化疗，对常规治疗已经产生了抵抗性，我们已经证明我们的制剂是有效的，”妇产科和生殖科教授桑廷说，他也是耶鲁大学附属斯米洛肿瘤医院妇科肿瘤项目研究组组长。
对于后续研究，萨尔茨曼教授说，他们会“调整”纳米颗粒的特性。例如，他们可以调整颗粒的粘附性，以及在靶向部位如何让颗粒快速释放药物。
以下为英文原文：
Fighting cancer with sticky nanoparticles
Sticky nanoparticles that deliver drugs precisely to their targets—and then stay there—could play a crucial role in fighting ovarian and uterine cancers.
A team of researchers at Yale found that a treatment using bioadhesive nanoparticles loaded with a potent chemotherapy drug proved more effective and less toxic than conventional treatments for gynecological cancer. The results of the work, led by professor Mark Saltzman at the Yale School of Engineering and Applied Science and professor Alessandro Santin at the Yale School of Medicine, appear Sept. 19 in the Proceedings of the National Academy of Sciences.
The nanoparticles are loaded with a drug known as epothilone B (EB) and injected into the peritoneal space, the fluid of the abdominal cavity. EB has been used in clinical trials to target tumor cells resistant to conventional chemotherapy agents. The drug proved effective in these trials, but severe side effects caused by the drug's high toxicity prevented further use.
The Yale Cancer Center researchers' treatment significantly reduces the drug's toxicity by encasing it in a nanoparticle that gradually releases the drug in high concentration at the cancer site. The problem with conventional nanoparticles, though, is that they are cleared from the target region too quickly to have much of an effect due to their small size, note the scientists.
"The challenge was to find a way to use that drug, which is very effective if you can keep it in the right place for a long enough period," said Saltzman, the Goizueta Foundation Professor of Biomedical and Chemical Engineering.
To that end, the Yale team developed nanoparticles covered with aldehyde groups, which chemically adhered to mesothelial cells in the abdominal cavity when injected into the peritoneum. Tested on mice with human tumors growing in their abdominal regions, the bioadhesive nanoparticles stayed in place for at least 24 hours. Non-adhesive nanoparticles injected into control mice began to leave the abdominal cavity after five minutes. Sixty percent of the mice receiving the treatment with the bioadhesive nanoparticles survived for four months—a significant improvement over mice in the control groups, where 10% or fewer lived as long.
By localizing the delivery of the drug, Santin said, they both decreased the toxicity of the drug and increased its effectiveness. This treatment could be particularly beneficial to patients with later stages of ovarian and uterine cancer, which is extremely difficult to treat due to how the cancer spreads in the peritoneal region, he said.
"They've been treated with surgery and chemotherapy and are now resistant to any standard treatment, and we've shown that this agent can be effective," said Santin, professor of obstetrics, gynecology, and reproductive sciences, and research team leader of the Gynecologic Oncology Program at Smilow Cancer Hospital at Yale New Haven.
For future studies, Saltzman said, they may "tune" the nanoparticles' properties. For instance, they can adjust the adhesiveness of the particles, and how quickly the particles release the drugs at the target site.
(来源：中国科技网)
