Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, SD 57104, USA.
Biomaterials. 2011 Mar;32(7):1890-905. doi: 10.1016/j.biomaterials.2010.11.028. Epub 2010 Dec 16.
We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy.
我们开发了一种多层方法来合成用于热疗、磁共振成像(MRI)和药物输送应用的水散超顺磁性氧化铁纳米粒子。在这种方法中,通过在氨存在下沉淀铁盐获得氧化铁核纳米粒子,并提供β-环糊精和泊洛沙姆聚合物(F127)涂层。这种制剂(F127250)具有高度的水分散性,允许将抗癌药物(s)封装在β-环糊精和泊洛沙姆聚合物中以实现持续的药物释放。与纯磁性纳米粒子(MNP)和β-环糊精包被的纳米粒子(CD200)相比,F127250 制剂在交变磁场下随时间表现出优越的热疗效果。此外,与 MNP 和 CD200 制剂相比,在琼脂凝胶中和顺铂耐药卵巢癌细胞(A12780CP)中也观察到 F127250 制剂的 MRI 特性得到改善。此外,F127250 的载药制剂表现出多倍的成像对比度特性。由于 F127250 制剂的内化能力,其负载姜黄素的制剂(F127250-CUR)对 A2780CP(卵巢)、MDA-MB-231(乳腺)和 PC-3(前列腺)癌细胞表现出几乎等效的抑制作用,尽管姜黄素释放仅为 40%。通过使用 Western blot 和透射电子显微镜(TEM)研究检查分子效应,验证了改善的治疗效果。F127250-CUR 还表现出良好的血液相容性,表明其是一种用于癌症治疗的纳米化疗剂。