【摘要】 目的观察及评价四氧化三铁（Fe₃O₄）-氧化石墨烯（GO）磁力定向纳米颗粒在乳腺癌化疗中的应用。方法制备Fe₃O₄-GO-阿霉素（DOX）复合物,检测其载药率及释药率。通过体内、体外实验观察、比较Fe₃O₄-GO-DOX与单纯DOX在载药定向、肿瘤抑制方面的优劣。结果 Fe₃O₄-GO-DOX载药率及释药率分别为84.2%、92.7%。以48 h为观察终点,Fe₃O₄-GO-DOX对MCF-7细胞的抑制显著优于DOX（DOX浓度为0.25、0.5及1μg/mL时,P<0.05）;以2周为观察终点,Fe₃O₄-GO-DOX与单纯DOX相比,治疗前后裸鼠肿瘤体积减少显著上调（50±13 vs. 23±7,P=0.022）。经尾静脉注射^99mTc标记的Fe₃O₄-GO-DOX或DOX的ECT结果显示:不同于^99mTc-DOX组荷瘤裸鼠相对弥散的肿瘤内^99mTc聚集,Fe₃O₄-GO-^99mTc-DOX组荷瘤裸鼠肿瘤内^99mTc聚集明显上调,且呈粗大的颗粒状分布。DOX治疗后4 h及24 h,与DOX组相比,Fe₃O₄-GO-DOX组瘤内^99mTc聚集显著增强（P<0.001）,而瘤旁^99mTc聚集显著减弱（P=0.002,4 h;P=0.035,24 h）。结论 Fe₃O₄-GO纳米颗粒可通过磁力定向、缓释两大优势充分发挥化疗药物作用,实现精准、持续、有效的乳腺癌细胞抑制与杀伤,有着深远的应用前景。更多还原

【Abstract】 Objective To observe and assess the application of magnetic targeted Fe₃O₄-graphene oxide（GO） nanoparticle in the chemotherapy of breast malignance. Methods A composite of Fe₃O₄, GO and Doxorubicin（DOX） was prepared and its loading and releasing rate was tested. A comparison between Fe₃O₄-GO-DOX and DOX alone was performed in the context of drug-targeting and tumor suppression both in vivo and in vitro. Results The loading and releasing rate of Fe₃O₄-GO-DOX were 84.2% and 92.7%, respectively. In vitro, the MCF-7 cellular inhibition rate was significantly higher in Fe₃O₄-GO-DOX group than that in DOX alone group when effective concentration of DOX were 0.25, 0.5 and 1 μg/mL till the end of 48 h incubation. In vivo, the decrease in the volume of tumor 2 weeks after treatment was significantly up-regulated in Fe₃O₄-GO-DOX group than that in DOX alone group（50±13 vs. 23±7, P=0.022）. ECT images, which presented the distribution of ^{99 m}Tc after a caudal vein injection of ^{99 m}Tc marked Fe₃O₄-GO-DOX or DOX alone, showed that in contrast to the scattered distribution of intra-tumor ^{99 m}Tc in DOX alone group, the distribution of intra-tumor ^{99 m}Tc in Fe₃O₄-GO-DOX group was significantly up-regulated and presented as a coarse dot. The intra-tumor distribution of ^{99 m}Tc was significantly up-regulated（P<0.001 for both 4 h and 24 h） and the extra-tumor distribution of ^{99 m}Tc was significantly down-regulated（P=0.002 for 4 h and P=0.035 for 24 h） in Fe₃O₄-GO-DOX group, in comparison to that in DOX alone group 4 h and 24 h after treatment. Conclusion With the merits of magnetic targeting and delayed release, Fe₃O₄-GO nanoparticle acts as a promising tool that might lead to precise, durable and effective tumor suppression in the chemotherapy of breast malignance.更多还原