Rice大学研究人员和Baylor医学院儿科专家最近，利用在Rice大学著名的buckyball纳米颗粒基础上，发明出一种将药物递送进癌细胞的全新方法。研究结果刊登于1月21日《Organic and Biomolecular Chemistry》杂志。
细胞壁和细胞膜是细胞的保护层。“如果药物能够通过细胞膜直接进入细胞，会更有效，”研究小组带头人Andrew Barron说，病毒很久以前就进化出一种穿过细胞壁的途径，我们可以模拟病毒的这些特征，利用蛋白的非毒性片段。
由Barron等人发展出的buckyball含有一种被称作Bucky（Baa）氨基酸的小分子。Bucky氨基酸位于pheylalanine（20种重要的氨基酸之上），如同珍珠穿在项链上，形成各种形式的蛋白。
Barron的研究生杨建中（Jianzhong Yang，音译），发明出几种含不同Baa的肽段或者是含有12个左右Baa的蛋白长条。天然状态下，pheylalanine作为将这些“珍珠”穿起来的链条，肽段不会穿过细胞防护层。
Barron小组与杨建中的兄弟——Baylor医学院副教授杨建华（Jianhua Yang，音译）合作，发现含Baa的肽段与病毒蛋白相似，能够穿过癌细胞的细胞膜，比如能够有效穿过肝癌活细胞和成神经细胞瘤活细胞的细胞膜。
成神经细胞瘤是最常见的儿童颅外实体肿瘤，占所有儿童致死性癌症的15％。杨建华说这项发现很有意义，因为成神经细胞瘤细胞很难通过细胞膜转染。Barron是Rice大学Charles W. Duncan Jr.-Welch化学教授、原料科学教授。
英文原文：
Buckyballs used as 'passkey' into cancer cells
Scientists at Rice University and Baylor College of Medicine have discovered a new way to use Rice's famed buckyball nanoparticles as passkeys that allows drugs to enter cancer cells.
The research appears in the Jan. 21 issue of the journal Organic and Biomolecular Chemistry.
All living cells defend themselves by walling off the outside world. Cell walls, or membranes, form a protective cocoon around the cell's inner machinery and its DNA blueprints.
"Drugs are far more effective if they're delivered through the membrane, directly into the cell," said lead researcher Andrew Barron. "Viruses, which are often toxic, long ago developed ways of sneaking through cell walls. While we're mimicking some techniques used by viruses, we're using non-toxic pieces of protein, and we're incorporating buckyballs as a passkey."
The passkeys that Barron and colleagues developed contain a molecule called Bucky amino acid that was created in Barron's lab. Bucky amino acid, or Baa, is based on pheylalanine, one of the 20 essential amino acids that are strung together like beads on a necklace to build all proteins.
Barron's graduate student, Jianzhong Yang, developed several different Baa-containing peptides, or slivers of protein containing about a dozen or so amino acids. In their natural form, with pheylalanine as a link in their chain, these peptides did not pass through the cell walls.
Barron's group collaborated with Yang's brother, Baylor College of Medicine assistant professor Jianhua Yang at Texas Children抯 Cancer Center, and found the Baa-containing peptides could mimick viral proteins and pass through the walls of cancer cells. The peptides were found effective at penetrating the defenses of both liver cancer cells and neuroblastoma cells.
"Neuroblastoma is the most common extracranial solid tumor in children, and it is responsible for about 15 percent of pediatric cancer deaths," said Jianhua Yang. "Our findings are significant because neuroblastoma cells are well-known for their difficulty in transfection through the cell membrane."
Barron is Rice's Charles W. Duncan Jr.-Welch Professor of Chemistry, professor of materials science and associate dean for industry interactions and technology transfer.
Co-authors include Rice undergraduate student Jonathan Driver and Baylor College of Medicine postdoctoral fellow Kuan Wang.
The research is supported by the Welch Foundation, the Bear Necessities Pediatric Cancer Foundation and the Hope Street Kids Foundation.
