南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (08): 891-.doi: 10.12122/j.issn.1673-4254.2019.08.03

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磁性纳米复合物PEG-APTES-MNP介导的磁热作用可有效抑制肝癌的生长

郑权,高鹏,李晓锋,李海量   

  • 出版日期:2019-08-20 发布日期:2019-08-20

Effects of magnetic thermotherapy mediated by magnetic nanocomposite PEG-APTESMNP on proliferation of liver cancer cells

  • Online:2019-08-20 Published:2019-08-20

摘要: 目的观察磁性纳米复合物PEG-APTES-MNP介导的磁热对肝癌的影响。方法合成磁性纳米粒子复合物,并将与肝癌细 胞HepG2共同孵育,并将其分为纳米粒磁热治疗组、纳米粒治疗组和对照组。普鲁氏蓝染色法检测HepG2细胞对磁性纳米粒 子的摄取效率;MTT法检及流式细胞术测磁性纳米粒子对HepG2的抑制效果;激光共聚焦检测磁性纳米粒子在细胞内产生活 性氧自由基(ROS)水平;将裸鼠植瘤,并将其分为PEG-APTES-MNP组(只注射磁性纳米复合物)、PEG-APTES-MNP(Heat)组 (注射磁性纳米复合物并进行磁热治疗)和对照组(注射等体积PBS),每组5只,分别进行治疗并检测其在动物水平对肿瘤的抑 制作用。结果合成的磁性纳米复物表征准确;血细胞凝集实验表明其不会引起血细胞的聚集,具有良好的理化性质和生物相 容性;在肿瘤细胞HepG2内可以产生大量活性氧自由基,在体外实验中协同磁热对其增殖产生了更强的抑制效果(P<0.05),并 促进细胞凋亡;在体内实验中,其介导磁热的作用下可以有效抑制肝癌动物模型肿瘤生长(P<0.05)。结论磁性纳米复合物 PEG-APTES-MNP具有良好的理化性质和生物相容性,其介导的磁热作用可有效抑制HepG2细胞及肝癌动物模型肿瘤生长, 可以作为肝癌的潜在纳米药物。

Abstract: Objective To observe the inhibitory effects of PEG-APTES-MNP magnetic heating on liver cancer cells. Methods The magnetic nanoparticle complex PEG-APTES-MNP was synthesized and its physiochemical properties and biocompatibility were characterized. HepG2 cells were incubated with the PEG-APTES-MNP nanoparticles for magnetic heating or nanoparticle therapy. Prussian blue staining was used to detect the uptake efficiency of the magnetic nanoparticles by HepG2 cells. MTT assay and flow cytometry were used to evaluate the inhibitory effect of the nanoparticles on HepG2 cells, and laser scanning confocal microscopy was used to detect the production of reactive oxygen species (ROS) in the cells. Fifteen nude mice bearing HepG2 cell xenografts were randomized equally into PEG-APTES-MNP injection group (with nanocomposite injection only), PEG-APTES-MNP magnetic heating group and control group (with PBS injection), and the tumor growth were observed in the mice after the treatments. Results The synthesized PEG-APTES-MNP nanoparticles showed good physicochemical properties and biocompatibility. Incubation of HepG2 with the nanoparticles resulted in significantly increased ROS production, obvious inhibition of the cell growth through the synergetic effects of magnetic heating (P<0.05), and significantly enhanced cell apoptosis. In the tumor-bearing nude mice, the nanoparticles strongly inhibited the tumor growth by magnetic heating (P<0.05). Conclusion The magnetic nanocomposite PEG-APTES-MNP has good physicochemical properties and bioavailability and can strongly inhibit the growth of liver cancer cells both in vitro and in nude mice through magnetic heating, demonstrating its potential as a candidate nanomedicine for liver cancer treatment.