Yang Cuiping, Xiong Fei, Wang Jing, Dou Jun, Chen Junsong, Chen Dengyu, Zhang Yu, Luo Shouhua, Gu Ning
Department of Pathogenic Biology & Immunology, Medical School, Southeast University, Nanjing 210009, China.
Nanomedicine (Lond). 2014 Jan;9(1):45-60. doi: 10.2217/nnm.12.216. Epub 2013 Mar 27.
To investigate the effects of anti-ABCG2 monoclonal antibodies (mAbs) in combination with paclitaxel iron oxide nanoparticles (PTX-NPs) on CD138(-)CD34(-) multiple myeloma (MM) cancer stem cells (CSCs) in JJN3 cells.
MATERIALS & METHODS: PTX-NPs were prepared using the hydrophobic interaction of the polyoxypropylene chain and oleic acid on the surface of iron oxide NPs and were targeted to the ABCG2 transporter overexpressing MM CSCs with mAbs.
The data showed that MM CSCs have strong drug resistance and tumorigenicity compared with non-MM CSCs. PTX-NPs combined with mAbs led to a significant reduction in the tumor volume, a visible alleviation of lytic bone lesions and a markedly increased survival rate in contrast to using a single agent in MM CSCs when it was transplanted to nonobese diabetic/severe combined immunodeficiency mice.
This study is the first to report on the anti-MM CSC activity by PTX-NPs as a single agent or used together with anti-ABCG2 mAbs to treat MM. These findings provide a rationale for future clinical trials.
研究抗ABCG2单克隆抗体（mAbs）联合紫杉醇氧化铁纳米颗粒（PTX-NPs）对JJN3细胞中CD138(-)CD34(-)多发性骨髓瘤（MM）癌干细胞（CSCs）的影响。
利用氧化铁纳米颗粒表面聚氧丙烯链与油酸的疏水相互作用制备PTX-NPs，并用mAbs靶向过表达ABCG2转运蛋白的MM CSCs。
数据显示，与非MM CSCs相比，MM CSCs具有很强的耐药性和致瘤性。当将其移植到非肥胖糖尿病/严重联合免疫缺陷小鼠体内时，与在MM CSCs中单独使用一种药物相比，PTX-NPs联合mAbs可显著减小肿瘤体积，明显减轻溶骨性骨病变，并显著提高存活率。
本研究首次报道了PTX-NPs作为单一药物或与抗ABCG2 mAbs联合使用治疗MM的抗MM CSC活性。这些发现为未来的临床试验提供了理论依据。
