Enhancement of Radiosensitization by Silver Nanoparticles Functionalized with Polyethylene Glycol and Aptamer As1411 for Glioma Irradiation Therapy
Enhancement of Radiosensitization by Silver Nanoparticles Functionalized with Polyethylene Glycol and Aptamer As1411 for Glioma Irradiation Therapy
复制标题
聚乙二醇和适体 As1411 功能化的银纳米粒子增强胶质瘤放射治疗的放射增敏作用
DOI：
10.2147/ijn.s224160
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发表时间：
2019
影响因子：
8
通讯作者：
Jiang Yaowen
中科院分区：
文献类型：
--
作者：
Zhao Jing;Liu Peidang;Ma Jun;Li Dongdong;Yang Huiquan;Chen Wenbin;Jiang Yaowen
背景胶质瘤细胞的放射耐药往往限制了放疗对胶质瘤的疗效。本课题组前期研究发现银纳米颗粒（AgNPs）对胶质瘤有放射增敏作用。为了增强肿瘤细胞的放射敏感性和选择性杀伤肿瘤细胞，同时减少放射治疗的副作用，迫切需要对AgNPs进行靶向修饰。本研究合成了聚乙二醇（PEG）和适体As1411 （AsNPs）功能化的AgNPs，并用透射电子显微镜、紫外-可见光谱和傅里叶变换红外光谱对其进行了表征。然后通过暗场成像、共聚焦显微镜和体内成像评价AsNPs的靶向性。采用集落形成实验和胶质瘤小鼠模型研究了AsNPs的放射增敏作用。结果表征结果显示AgNPs为球形，平均直径为18 nm，并成功构建了AsNPs。AsNPs被证实特异性靶向C6胶质瘤细胞，而不是正常的人微血管内皮细胞。此外，AsNPs不仅可以内化到肿瘤细胞中，还可以渗透到肿瘤球体的核心。体外实验表明，AsNPs比AgNPs和PEGylated AgNPs （PNPs）具有更好的放射增敏作用，诱导更高的凋亡细胞死亡率。体内成像显示，Cy5-AsNPs优先在肿瘤部位积累，且全身给药后6 h， Cy5-AsNPs与Cy5-PNPs的荧光强度之比达到最大。此外，AsNPs联合照射可显著延长C6胶质瘤小鼠的中位生存时间。结论AsNPs可能是一种有效的靶向治疗胶质瘤的纳米放射增敏剂。
Background The efficacy of radiotherapy for glioma is often limited by the radioresistance of glioma cells. The radiosensitizing effects of silver nanoparticles (AgNPs) on glioma were found in the previous studies of our group. In order to enhance the radiosensitivity of tumor cells and selectively kill them while reducing the side effects of irradiation therapy, targeted modification of AgNPs is urgently needed. Materials and methods In the present study, AgNPs functionalized with polyethylene glycol (PEG) and aptamer As1411 (AsNPs) were synthesized and subsequently characterized by transmission electron microscopy, ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. Then the targeting property of AsNPs was evaluated by dark-field imaging, confocal microscopy and in vivo imaging. Both colony formation assay and glioma-bearing mouse model were employed to study the radiosensitizing effect of AsNPs. Results The characterization results revealed a spherical shape of AgNPs with an average diameter of 18 nm and the successful construction of AsNPs. AsNPs were confirmed to specifically target C6 glioma cells, but not normal human microvascular endothelial cells. Moreover, AsNPs could not only internalize into tumor cells, but also penetrate into the core of tumor spheroids. In vitro experiments showed that AsNPs exhibited a better radiosensitizing effect than AgNPs and PEGylated AgNPs (PNPs), inducing a higher rate of apoptotic cell death. In vivo imaging demonstrated that Cy5-AsNPs preferentially accumulated at the tumor site, and the ratio of fluorescence intensity of Cy5-AsNPs to that of Cy5-PNPs reached the maximum at 6 h post-systemic administration. Furthermore, the combination of AsNPs with irradiation significantly prolonged the median survival time of C6 glioma-bearing mice. Conclusion Our results indicated that AsNPs could be an effective nano-radiosensitizer for glioma targeting treatment.