碳包铁纳米颗粒结合贝伐单抗治疗裸鼠肝癌

Effect of nanoparticle conjugated with bevacizumab in liver cancer

目的观察碳包铁纳米颗粒结合贝伐单抗靶向治疗肝癌的效果。方法将SSMC7721细胞注入裸鼠背部皮下，以建立鼠肝癌模型。40只荷瘤裸鼠随机分为5组，每组8只。A组为对照组，通过鼠尾静脉注射等量生理盐水（NS），B组注射盐酸表阿霉素（Ep），C组注射贝伐单抗（Bm），D组注入结合贝伐单抗的碳包铁纳米颗粒（BMN），E组注射碳包铁纳米颗粒生理盐水分散液（Fe@C），D、E组均在肿瘤表面每天接受1次场强为3000Gauss的磁场作用，时间30min。所有裸鼠在实验7d后脱颈处死，取肿瘤组织行苏木素一伊红（HE）染色，原位缺口末端标记法（TUNEL）法检测凋亡，免疫组织化学观测肿瘤内微血管密度。结果Ep组和BMN组可以明显的肿瘤抑制，两组凋亡指数分别为（73．3±8．0）％和（63．1±7．0）％，差异无统计学意义（P〉0．05）。BMN组的肿瘤微血管密度为21．75±3．96，而Bm组为40．25±3．85。BMN组的凋亡指数和微血管密度与其他组比较均有差异有统计学意义（P〈0．05）。结论BMN在外界磁场的作用下，可以使贝伐单抗更好地发挥肿瘤抑制作用，减少化疗期间的不良反应。

Objective To observe the targeted biodistribution of carbon - coated pure iron core （ Fe@ C） magnetic anoparticles, conjugated with bevacizumab （BMN） in liver cancer xenografts. Methods SSMC7721 cells were subcutaneously inoculated into the posterior flank. All mice were randomly divided into five groups （n = 8 for each group）. Group A, control group, was injected with normal saline through the tail vein. Mice in groups B and C were injected with epirubicin and BMN respectively through the tail vein. Groups D and E were injected with BMN and Fe@ C without BMN respectively. Both groups D and E were subjected to a magnetic field at 3 000 gauss bulit on the surface of tumor for 30 min once a day. All mice were euthanized after treatment for 7 days. The tumors were resected. Following staining with hema- toxylin and eosin （ HE）, tumor specimens from all groups were examined for apoptosis by a TdT - mediated dUTP nick end labeling （TUNEL） assay. The microvessel density （MVD） was evaluated by immunohisto- chemistry. Results The complete tumor suppression was observed in groups B and D. The apoptotic index in groups B and D was （73.3 ±8.0）% and （63.1 ±7.0）% , respectively （P〉0.01）. The MVD was decreased to 21.75 ± 3.96 in group D and 40. 25 ± 3.85 in group C （ P 〈 0.05 ）. There was significant difference between group D and other groups. Conclusion This study indicated the possibility of BMN preparation and treatment for tumor. BMN may play an important role in tumoricidal effect.