Rice大學研究人員和Baylor醫(yī)學院兒科專家最近,,利用在Rice大學著名的buckyball納米顆粒基礎上,,發(fā)明出一種將藥物遞送進癌細胞的全新方法,。研究結(jié)果刊登于1月21日《Organic and Biomolecular Chemistry》雜志。
細胞壁和細胞膜是細胞的保護層,。“如果藥物能夠通過細胞膜直接進入細胞,,會更有效,”研究小組帶頭人Andrew Barron說,,病毒很久以前就進化出一種穿過細胞壁的途徑,我們可以模擬病毒的這些特征,,利用蛋白的非毒性片段,。
由Barron等人發(fā)展出的buckyball含有一種被稱作Bucky(Baa)氨基酸的小分子。Bucky氨基酸位于pheylalanine(20種重要的氨基酸之上),,如同珍珠穿在項鏈上,,形成各種形式的蛋白。
Barron的研究生楊建中(Jianzhong Yang,,音譯),,發(fā)明出幾種含不同Baa的肽段或者是含有12個左右Baa的蛋白長條。天然狀態(tài)下,,pheylalanine作為將這些“珍珠”穿起來的鏈條,,肽段不會穿過細胞防護層。
Barron小組與楊建中的兄弟——Baylor醫(yī)學院副教授楊建華(Jianhua Yang,音譯)合作,,發(fā)現(xiàn)含Baa的肽段與病毒蛋白相似,,能夠穿過癌細胞的細胞膜,比如能夠有效穿過肝癌活細胞和成神經(jīng)細胞瘤活細胞的細胞膜,。
成神經(jīng)細胞瘤是最常見的兒童顱外實體腫瘤,,占所有兒童致死性癌癥的15%。楊建華說這項發(fā)現(xiàn)很有意義,,因為成神經(jīng)細胞瘤細胞很難通過細胞膜轉(zhuǎn)染,。Barron是Rice大學Charles W. Duncan Jr.-Welch化學教授、原料科學教授,。
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.