Department of Polymer Particles, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06, Prague 6, Czech Republic.
Department of Biological Models, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06, Prague 6, Czech Republic.
Chempluschem. 2020 Jun;85(6):1156-1163. doi: 10.1002/cplu.202000360.
Development of therapeutic systems to treat glioblastoma, the most common and aggressive brain tumor, belongs to priority tasks in cancer research. We have synthesized colloidally stable magnetic nanoparticles (D =336 nm) coated with doxorubicin (Dox) conjugated copolymers of N,N-dimethylacrylamide and either N-acryloylglycine methyl ester or N-acryloylmethyl 6-aminohexanoate. The terminal carboxyl groups of the copolymers were reacted with alendronate by carbodiimide formation. Methyl ester groups were then transferred to hydrazides for binding Dox by a hydrolytically labile hydrazone bond. The polymers were subsequently bound on the magnetic nanoparticles through bisphosphonate terminal groups. Finally, the anticancer effect of the Dox-conjugated particles was investigated using the U-87 glioblastoma cell line in terms of particle internalization and cell viability, which decreased to almost zero at a concentration of 100 μg of particles per ml. These results confirmed that poly(N,N-dimethylacrylamide)-coated magnetic nanoparticles can serve as a solid support for Dox delivery to glioblastoma cells.
开发治疗脑胶质瘤(最常见和最具侵袭性的脑肿瘤)的治疗系统属于癌症研究的重点任务。我们合成了胶体稳定的磁性纳米颗粒(D = 336nm),表面涂有阿霉素(Dox)偶联的 N,N-二甲基丙烯酰胺共聚物,以及 N-丙烯酰基甘氨酸甲酯或 N-丙烯酰基甲基 6-氨基己酸酯。共聚物的末端羧基通过碳二亚胺形成与阿仑膦酸钠反应。然后将甲酯基团转化为酰腙,通过水解不稳定的腙键结合 Dox。聚合物通过双膦酸盐末端基团结合到磁性纳米颗粒上。最后,使用 U-87 脑胶质瘤细胞系研究了 Dox 偶联颗粒的抗癌作用,包括颗粒内化和细胞活力,当浓度达到每毫升 100μg 颗粒时,细胞活力几乎降为零。这些结果证实,聚(N,N-二甲基丙烯酰胺)包覆的磁性纳米颗粒可用作向脑胶质瘤细胞递送 Dox 的固体载体。