Azadbakht Bakhtiar, Afarideh Hossein, Ghannadi-Maragheh Mohammad, Bahrami-Samani Ali, Asgari Mehdi
Department of Energy Engineering and Physics, Amirkabir University of Technology, 15875-4413 Tehran, Iran.
Department of Energy Engineering and Physics, Amirkabir University of Technology, 15875-4413 Tehran, Iran.
Nucl Med Biol. 2017 May;48:26-30. doi: 10.1016/j.nucmedbio.2016.05.002. Epub 2016 May 6.
Radioimmuno-conjugated (Rhenium-188 labeled Rituximab), 3-aminopropyltriethoxysilane (APTES)-polyethylene glycol (PEG) coated iron oxide nanoparticles were synthesized and then characterized. Therapeutic effect and targeting efficacy of complex were evaluated in CD20 express B cell lines and tumor bearing Balb/c mice respectively. To reach these purposes, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using coprecipitation method and then their surface was treated with APTES for increasing retention time of SPIONs in blood circulation and amine group creation. In the next step, N-hydroxysuccinimide (NHS) ester of polyethylene glycol maleimide (NHS-PEG-Mal) was conjugated to the APTES-treated SPIONs. After radiolabeling of Rituximab antibody with Rhenium-188 (T=16.9h) using synthesized NS chelator, it was attached to the APTES-PEG-MAL-SPIONs surface through thiol-maleimide coupling reaction. In vitro evaluation of the ReNS-Rituximab-SPION-complex thus obtained revealed that at 24 and 48h post-treatment effective cancer cell killing had been achieved. Bio-distribution study in tumor bearing mice showed capability of this complex for targeted cancer therapy. Active and passive tumor targeting strategies were applied through incorporated anti-CD20 (Rituximab) antibody and also enhanced permeability and retention (EPR) effect of solid tumors for nanoparticles respectively.
合成并表征了放射性免疫偶联物（铼 - 188标记的利妥昔单抗）、3 - 氨丙基三乙氧基硅烷（APTES） - 聚乙二醇（PEG）包覆的氧化铁纳米颗粒。分别在CD20表达的B细胞系和荷瘤Balb/c小鼠中评估了该复合物的治疗效果和靶向效能。为实现这些目的，采用共沉淀法合成了超顺磁性氧化铁纳米颗粒（SPIONs），然后用APTES处理其表面，以增加SPIONs在血液循环中的保留时间并产生胺基。下一步，将聚乙二醇马来酰亚胺的N - 羟基琥珀酰亚胺（NHS）酯（NHS - PEG - Mal）偶联到经APTES处理的SPIONs上。使用合成的NS螯合剂用铼 - 188（T = 16.9小时）对利妥昔单抗抗体进行放射性标记后，通过硫醇 - 马来酰亚胺偶联反应将其连接到APTES - PEG - MAL - SPIONs表面。对由此获得的ReNS - 利妥昔单抗 - SPION复合物进行的体外评估显示，在处理后24小时和48小时实现了有效的癌细胞杀伤。在荷瘤小鼠中的生物分布研究表明该复合物具有靶向癌症治疗的能力。分别通过掺入抗CD20（利妥昔单抗）抗体以及利用实体瘤对纳米颗粒的高通透性和滞留（EPR）效应，应用了主动和被动肿瘤靶向策略。
