Laboratory of Nanomedicine, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023, Orissa, India.
Biomaterials. 2010 May;31(13):3694-706. doi: 10.1016/j.biomaterials.2010.01.057. Epub 2010 Feb 7.
The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy.
化疗药物的主要缺陷在于其相对的非特异性和对健康组织的潜在副作用。为了克服这一问题,人们设计了载药多功能磁性纳米粒子。我们在此报告了一种基于甘油单油酸酯(GMO)包覆的磁性纳米粒子(GMO-MNPs)的水性制剂,该制剂不含任何表面活性剂,却能够负载高载量的疏水性抗癌药物。通过肿瘤坏死因子-α测定法和共聚焦显微镜证实了其生物相容性。在体外条件下,不同的抗癌药物(紫杉醇、雷帕霉素、单独或联合)的包封药物的包封效率高达 95%左右,并且能够持续释放两周以上。负载药物的 GMO-MNPs 不会影响氧化铁核的磁化特性,这一点通过磁化研究得到了证实。此外,通过用 DMSA(二巯丁二酸)包覆,MNPs 被官能化上了羧基,以便进一步与胺类进行补充共轭。为了进行靶向治疗,将 HER2 抗体与 GMO-MNPs 共轭,并在人乳腺癌细胞系(MCF-7)中显示出增强的摄取。IC(50)剂量显示出对 MCF-7 的潜在抗增殖作用。因此,抗体共轭的 GMO-MNPs 可用作癌症治疗中主动治疗方面的潜在药物载体。