Dag Aydan, Jiang Yanyan, Karim Khairil Juhanni Abd, Hart-Smith Gene, Scarano Wei, Stenzel Martina H
Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093, Fatih, Istanbul, Turkey.
Macromol Rapid Commun. 2015 May;36(10):890-7. doi: 10.1002/marc.201400576. Epub 2015 Mar 19.
The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers N-(2-hydroxypropyl)methacrylamide (HPMA) and Boc protected 1,3-diaminopropan-2-yl acrylate (Ac-DAP-Boc) are copolymerized in the presence of a furan protected maleimide functionalized reversible addition-fragmentation chain transfer (RAFT) agent. The resulting polymer with a composition of P(HPMA14 -co-(Ac-DAP-Boc)9 ) and a molecular weight of Mn = 7600 g mol(-1) (Đ = 1.24) is used as a macromolecular ligand for the conjugation to the platinum drug. Thermogravimetric analysis reveals full conjugation. After deprotection of the maleimide functionality of the polymer, the reactive polymer is conjugated to albumin using the Cys34 functionality. The conjugation is monitored using size exclusion chromatography, MALDI-TOF (matrix assisted laser desorption ionization time-of-flight), and SDS Page (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The polymer-albumin conjugates self-assemble in water into nanoparticles of sizes of around 80 nm thanks to the hydrophobic nature of the platinum drugs. The albumin coated nanoparticles are readily taken up by ovarian cancer cell lines and they show superior toxicity compared to a control sample without protein coating.
通过将聚合物与白蛋白偶联，可增强大分子铂类药物进入癌细胞的能力。单体N-(2-羟丙基)甲基丙烯酰胺(HPMA)和Boc保护的1,3-二氨基丙烷-2-基丙烯酸酯(Ac-DAP-Boc)在呋喃保护的马来酰亚胺功能化可逆加成-断裂链转移(RAFT)剂存在下共聚。所得组成是P(HPMA14 -co-(Ac-DAP-Boc)9 )、分子量为Mn = 7600 g mol(-1)(Đ = 1.24)的聚合物用作与铂类药物偶联的大分子配体。热重分析显示完全偶联。聚合物的马来酰亚胺官能团脱保护后，使用Cys34官能团将反应性聚合物与白蛋白偶联。使用尺寸排阻色谱、基质辅助激光解吸电离飞行时间(MALDI-TOF)和十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS Page)监测偶联情况。由于铂类药物的疏水性，聚合物-白蛋白偶联物在水中自组装成尺寸约为80 nm的纳米颗粒。包被白蛋白的纳米颗粒很容易被卵巢癌细胞系摄取，并且与没有蛋白质包被的对照样品相比，它们显示出更高的毒性。
