| 李承霞,李玮,张富海,贾强,李宁,常津,季艳会,谭建.131I标记抗表皮生长因子受体抗体靶向性纳米载体治疗胶质母细胞瘤的可行性实验研究[J].中华放射医学与防护杂志,2016,36(3):161-167 |
| 131I标记抗表皮生长因子受体抗体靶向性纳米载体治疗胶质母细胞瘤的可行性实验研究 |
| Targeting therapeutic effect of radioiodine-labeled anti-EGFR binding nanoparticles on glioblastoma cells |
| 投稿时间：2015-08-03 |
| DOI：10.3760/cma.j.issn.0254-5098.2016.03.001 |
| 中文关键词: 纳米载体 放射碘标记 表皮生长因子受体抗体 131I |
| 英文关键词:Nanoparticles Radioiodine-labeled cells Epidermal growth factor receptor antibody 131I |
| 基金项目:国家自然科学基金(81301244) |
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| 摘要点击次数: 3645 |
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| 中文摘要: |
| 目的 构建131I标记抗表皮生长因子受体抗体(antiEGFR)靶向性的纳米载体,探讨其在细胞水平和动物体内用于胶质瘤治疗的可行性。方法 制备放射性碘(131I)标记的antiEGFR靶向性的纳米载体牛血清白蛋白聚己内酯复合物131I-antiEGFR-BSA-PCL。用共聚焦显微镜观察纳米载体能够与肿瘤细胞结合情况,用MTT法检测纳米载体的细胞毒性作用,摄碘率实验检测肿瘤细胞对放射性纳米载体的摄取。制备裸鼠种植瘤模型,通过瘤体内注射给药,观察裸鼠种植瘤的体积变化,通过SPECT显像观察药物在裸鼠体内的停留情况,并分析纳米载体在裸鼠体内的分布情况。结果 成功地制备了BSA-PCL及antiEGFR-BSA-PCL纳米载体。与BSA-PCL相比,antiEGFR-BSA-PCL更容易与肿瘤细胞结合。当放射性纳米载体的放射性活度达到0.925 MBq时,U251和U87细胞的生长抑制率131I-antiEGFR-BSA-PCL组均高于131I-BSA-PCL组(t=2.517、2.821,P<0.05),且均高于同组其他剂量(U251:t=2.148、2.693,P<0.05;U87:t=2.436、2.615,P<0.05)。裸鼠体内实验发现两种纳米载体瘤体内注射后均经过肝脏代谢。131I-antiEGFR-BSA-PCL组荷瘤裸鼠的种植瘤体积较131I-BSA-PCL组缩小更多(t=4.115,P<0.05)。结论 131I-antiEGFR-BSA-PCL在体内外实验中均能够抑制胶质瘤生长,为胶质瘤的治疗和预后评估提供了一种新方法。 |
| 英文摘要: |
| Objective To explore the feasibility of treating glioma with 131I-labeled antiEGFR nanoparticales in vitro and in vivo. Methods Radioiodine-labeled anti-EGFR binding nanoparticles were constructed and its in vitro cell-binding ability was confirmed by confocal microscopy and flow cytometry. Cell cytotoxicity of the drug was evaluated by MTT assay. Radioiodine-imaging studies were conducted by using a xenograft nude mouse model in vivo by detecting the change of the volume of the xenograft. ResultsIn vitro studies revealed that the anti-EGFR nanoparticles binding with bovine serum albumin-polycaprolactone (anti EGFR-BSA-PCL) or BSA-PCL were successfully constructed. Cells could uptake 131I-antiEGFR-BSA-PCL much more effectively than the 131I-BSA-PCL group. MTT assay indicated that, when the radioactivity approached to 0.925 MBq, the cell growth inhibition rate of 131I-antiEGFR-BSA-PCL was higher than that of 131I-BSA-PCL (U251 cells: t=2.517, P<0.05; U87 cells: t=2.821, P<0.05). The growth inhibition rates at 0.925 MBq was higher than other radioactivity in both U251 cells and U87 cells (131I-antiEGFR-BSA-PCL group: t=2.148, 2.436, P<0.05; 131I-BSA-PCL group: t=2.693, 2.615, P<0.05). Radioactive iodine uptake assay showed that the viability of U251 and U87 cells was reduced after exposure to 0.37 MBq to 3.7 MBq of 131I-antiEGFR-BSA-PCL or 131I-BSA-PCL. The in vivo nude mice experiments disclosed that both kinds of nanoparticles passed by the hepatic metabolism, and the decrease of tumor volume in the group of 131I-antiEGFR-BSA-PCL was more effective than that in the 131I-BSA-PCL group (t=4.115, P<0.05). EGFR significantly enhanced the uptake and accumulation of BSA-PCL in the xenografts nude mice model, indicating an improved nanoparticle-based drug delivery. Conclusions 131I-antiEGFR-BSA-PCL based radioiodine therapy of U251 and U87 cells had good curative effect in vitro and in vivo. Thus, 131I-antiEGFR-BSA-PCL may provide a new method for glioblastoma treatment. |
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