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目的探讨~(188)Re-Herceptin-磁性纳米微粒在外置磁场下对 HER-2/neu 癌基因高表达的SKBR-3乳腺癌细胞的靶向结合性及抗癌作用。方法采用戊二醛交联法使人源性单克隆抗体 Her-ceptin 与磁性纳米微粒交联,用直接标记法制备~(188)Re-Herceptin 及~(188)Re-Herceptin-磁性纳米微粒,用羰基铼标记法制备~(188)Re-磁性纳米微粒。肿瘤细胞体外抑制实验设4个组:~(188)Re-Herceptin-磁性纳米微粒组、~(188)Re-Herceptin 组、~(188)Re-磁性纳米微粒组和~(188)ReO_4~-组,各组均设3.7×10~4、18.5×10~4、37×10~4、55.5×10~4、74×10~4 Bq/ml 5个放射性剂量级别;另设生理盐水对照组。采用四甲基偶氮唑蓝(MTT)法测定各组的抑瘤效应,计算相对抑制率,采用半数抑制放射性浓度(IC_(50))对各组抑瘤作用进行比较和评价。结果 ~(188)Re-Herceptin-磁性纳米微粒和~(188)Re-Herceptin 组对 SKBR-3细胞均有较强杀伤作用,且呈剂量依赖性;而~(188)Re-磁性纳米微粒和~(188)ReO_4~-组的杀伤作用较弱。~(188)Re-Herceptin-磁性纳米微粒组的 IC_(50)(53.1×10~4 Bq/L)明显低于~(188)Re-Herceptin 组(76.1×10~4 Bq/L);~(188)Re-磁性纳米微粒组和~(188)ReO_4~-组的 IC_(50)分别为169×10~4和175×10~4 Bq/L,明显高于前2组。结论 ~(188)Re-Herceptin-磁性纳米微粒和~(188)Re-Herceptin 均可明显抑制体外培养的 SKBR-3乳腺癌细胞增殖,且前者的抑制作用较后者强。
Objective To investigate the targeted binding of ~ (188) Re-Herceptin-magnetic nanoparticles to SKBR-3 breast cancer cells with high HER-2 / neu oncogene under external magnetic field. Methods The human monoclonal antibody Her-ceptin was crosslinked with glutaraldehyde by glutaraldehyde cross-linking method, and 188 Re-Herceptin and 188 Re-Herceptin-magnetic nanoparticles were prepared by direct labeling method. ~ (188) Re - magnetic nanoparticles were prepared by carbonyl rhenium labeling. In vitro inhibition experiments of tumor cells were divided into four groups: ~ (188) Re-Herceptin-magnetic nanoparticle group, 188 Re-Herceptin group, 188 Re-magnetic nanoparticle group and 188 ReO 4 ~ Group, each group were set 5 radioactive doses of 3.7 × 10 ~ 4, 18.5 × 10 ~ 4, 37 × 10 ~ 4,55.5 × 10 ~ 4,74 × 10 ~ 4 Bq / ml; another saline control group . The anti-tumor effect of each group was determined by MTT method, and the relative inhibition rate was calculated. The inhibitory effect of each group was compared and evaluated by half inhibitory radioactive concentration (IC 50). Results ~ (188) Re-Herceptin-magnetic nanoparticle and ~ (188) Re-Herceptin group had stronger killing effect on SKBR-3 cells in a dose- ~ (188) ReO_4 ~ - group killing effect is weak. IC 50 (53.1 × 10 4 Bq / L) in ~ (188) Re-Herceptin-magnetic nanoparticle group was significantly lower than that in 188 Re-Herceptin group (76.1 × 10 -4 Bq / L) (188) Re-magnetic nanoparticle group and ~ (188) ReO_4 ~ - group were 169 × 10 ~ 4 and 175 × 10 ~ 4 Bq / L, respectively, which were significantly higher than those of the first two groups. Conclusion ~ (188) Re-Herceptin-magnetic nanoparticles and ~ (188) Re-Herceptin can significantly inhibit the proliferation of SKBR-3 breast cancer cells cultured in vitro, and the former inhibition is stronger than the latter.