纳米级三氧化二砷/三氧化二铁复合物联合磁流体热疗可选择性靶向肝癌细胞。
Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells.
作者信息
Wang Zi-Yu, Song Jian, Zhang Dong-Sheng
机构信息
School of Basic Medical Sciences, Southeast University, Nanjing, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2009 Jun 28;15(24):2995-3002. doi: 10.3748/wjg.15.2995.
AIM
To study the methods of preparing the magnetic nano-microspheres of Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes and their therapeutic effects with magnetic fluid hyperthermia (MFH).
METHODS
Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed. Hemolysis, micronucleus, cell viability, and LD(50) along with other in vivo tests were performed to evaluate the Fe(2)O(3) microsphere biocompatibility. The inhibition ratio of tumors after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated.
RESULTS
Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope. Upon exposure to an alternating magnetic field (AMF), the temperature of the suspension of magnetic particles increased to 41-51 degrees C, depending on different particle concentrations, and remained stable thereafter. Nanosized Fe(2)O(3) microspheres are a new kind of biomaterial without cytotoxic effects. The LD(50) of both Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) in mice was higher than 5 g/kg. One to four weeks after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complex injections into healthy pig livers, no significant differences were found in serum AST, ALT, BUN and Cr levels among the pigs of all groups (P > 0.05), and no obvious pathological alterations were observed. After exposure to alternating magnetic fields, the inhibition ratio of the tumors was significantly different from controls in the Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) groups (68.74% and 82.79%, respectively; P < 0.01). Tumors of mice in treatment groups showed obvious necrosis, while normal tissues adjoining the tumor and internal organs did not.
CONCLUSION
Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore, nanospheres are ideal carriers for tumor-targeted therapy.
目的
研究Fe₂O₃及As₂O₃/Fe₂O₃复合物磁性纳米微球的制备方法及其磁流体热疗（MFH）的治疗效果。
方法
采用化学共沉淀法制备纳米球并观察其形状和直径。进行溶血、微核、细胞活力及半数致死量（LD₅₀）等体内试验以评估Fe₂O₃微球的生物相容性。计算在人肝癌异种移植模型中注射Fe₂O₃和As₂O₃/Fe₂O₃并联合诱导热疗后肿瘤的抑制率。
结果
透射电子显微镜下观察到Fe₂O₃和As₂O₃/Fe₂O₃颗粒呈圆形，平均直径分别为20 nm和100 nm。暴露于交变磁场（AMF）后，磁性颗粒悬浮液的温度根据不同颗粒浓度升高至41 - 51℃，并在此后保持稳定。纳米级Fe₂O₃微球是一种无细胞毒性作用的新型生物材料。Fe₂O₃和As₂O₃/Fe₂O₃在小鼠体内的LD₅₀均高于5 g/kg。将Fe₂O₃和As₂O₃/Fe₂O₃复合物注射到健康猪肝脏1至4周后，所有组猪的血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、尿素氮（BUN）和肌酐（Cr）水平无显著差异（P > 0.05），且未观察到明显的病理改变。暴露于交变磁场后，Fe₂O₃组和As₂O₃/Fe₂O₃组肿瘤的抑制率与对照组有显著差异（分别为68.74%和82.79%；P < 0.01）。治疗组小鼠的肿瘤出现明显坏死，而肿瘤周围的正常组织和内脏未出现坏死。
结论
Fe₂O₃和As₂O₃/Fe₂O₃复合物对肿瘤具有射频诱导热疗和药物毒性作用，且无任何肝肾损伤。因此，纳米球是肿瘤靶向治疗的理想载体。
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