Li Xue-Song, Li Wei-Qing, Wang Wen-Bo
Department of Orthopedics, First Hospital of Harbin Medical University, Harbin, China.
Cancer Biother Radiopharm. 2007 Dec;22(6):772-8. doi: 10.1089/cbr.2007.352.
The present study was to investigate the therapeutic efficacy of the magnetic arsenic trioxide (ATO) nanoparticles against osteosarcoma in vivo tumor models. ATO was incorporated in the magnetic nanoparticles and encapsulated by poly lactic acid. Human MG-63 osteosarcoma cells were injected subcutaneously into the nude mice. After 15 days, the mice were randomly assigned to the four groups (n=6 mice): group 1: control, saline only (10 mL kg(-1) day(-1), intravenously (i.v.)); group 2: ATO alone (5 mg kg(-1) day(-1), i.v.); group 3: magnetic ATO nanoparticles at a dose equivalent to 50% of the ATO alone, with an external magnetic field on the tumor; group 4: CDDP, cisplatin (5 mg kg(-1) day(-1), i.v.). The mice were sacrificed after 21 days. In vitro release profiles showed that ATO was released rapidly from the nanoparticles. The magnetic ATO evaluation indicated that the magnetic nanoparticles might localize under the magnet in vivo. The tumor volume examination showed that the treatment with magnetic ATO nanoparticles achieved the similar inhibition effect on osteosarcoma as that of CDDP or ATO alone. Electron microscopic features typical of apoptosis were identified in the tumor tissue with the three-drug treatment. This "magnetic ATO targeting" offers an opportunity to treat osteosarcoma with a lower dose.
本研究旨在探讨磁性三氧化二砷（ATO）纳米颗粒在体内肿瘤模型中对骨肉瘤的治疗效果。ATO被掺入磁性纳米颗粒中，并由聚乳酸包裹。将人MG-63骨肉瘤细胞皮下注射到裸鼠体内。15天后，将小鼠随机分为四组（每组n = 6只小鼠）：第1组：对照组，仅注射生理盐水（10 mL·kg⁻¹·天⁻¹，静脉注射）；第2组：单独使用ATO（5 mg·kg⁻¹·天⁻¹，静脉注射）；第3组：磁性ATO纳米颗粒，剂量相当于单独使用ATO的50%，并在肿瘤部位施加外部磁场；第4组：顺铂（CDDP，5 mg·kg⁻¹·天⁻¹，静脉注射）。21天后处死小鼠。体外释放曲线表明ATO从纳米颗粒中快速释放。磁性ATO评估表明磁性纳米颗粒在体内可能会定位在磁体下方。肿瘤体积检查显示，磁性ATO纳米颗粒治疗对骨肉瘤的抑制效果与单独使用CDDP或ATO相似。在三种药物治疗的肿瘤组织中发现了典型的凋亡电子显微镜特征。这种“磁性ATO靶向”为以较低剂量治疗骨肉瘤提供了机会。
