Increasing the accumulation of aptamer AS1411 and verapamil conjugated silver nanoparticles in tumor cells to enhance the radiosensitivity of glioma

Increasing the accumulation of aptamer AS1411 and verapamil conjugated silver nanoparticles in tumor cells to enhance the radiosensitivity of glioma
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增加肿瘤细胞内适体AS1411和维拉帕米缀合银纳米粒子的积累,增强胶质瘤的放射敏感性

DOI:
10.1088/1361-6528/abd20a
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发表时间:
2020-12
期刊:
影响因子:
3.5
通讯作者:
Peidang Liu
Peidang Liu
中科院分区:
材料科学3区
文献类型:
--
作者:
Jing Zhao;Dongdong Li;Jun Ma;Huiquan Yang;Wenbin Chen;Yuyu Cao;Peidang Liu

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放射耐药显著降低放疗疗效,最终导致肿瘤复发和转移。作为一种新型的纳米放射增敏剂,银纳米颗粒(AgNPs)在胶质瘤放射治疗中显示出良好的放射增敏性能,但其有效进入肿瘤细胞并在肿瘤细胞内积累的能力有待提高。本研究合成并表征了AS1411和维拉帕米(VRP)偶联牛血清白蛋白(BSA)包被AgNPs (AgNPs@BSA-AS-VRP)。采用暗场成像和电感耦合等离子体质谱法研究不同比例混合的AgNPs@BSA-AS和AgNPs@BSA-AS-VRP在U251胶质瘤细胞中的积累情况。采用罗丹明123积累试验研究19:1混合AgNPs@BSA-AS和AgNPs@BSA-AS-VRP对p -糖蛋白(P-gp)外排活性的影响。采用集落形成实验和荷瘤裸鼠模型检测19:1混合AgNPs@BSA-AS和AgNPs@BSA-AS-VRP的放射致敏潜能。采用硫氧还蛋白还原酶(TrxR)测定试剂盒检测不同功能修饰AgNPs处理细胞后TrxR活性。表征结果表明,AgNPs@BSA-AS-VRP成功构建。当AgNPs@BSA-AS和AgNPs@BSA-AS-VRP以19:1的比例混合时,通过as1411介导的活性靶向和P-gp活性的抑制,细胞内纳米颗粒的数量大大增加。体外和体内实验清楚地表明,19:1混合AgNPs@BSA-AS和AgNPs@BSA-AS-VRP的放射增敏效果明显强于AgNPs@BSA和AgNPs@BSA-AS。还发现19:1混合AgNPs@BSA-AS和AgNPs@BSA-AS-VRP显著抑制细胞内TrxR活性。这些结果表明,19:1混合AgNPs@BSA-AS和AgNPs@BSA-AS-VRP可以有效地在肿瘤细胞中积累,在胶质瘤放疗中作为高效纳米放射增敏剂具有很大的潜力。
Radioresistance significantly decreases the efficacy of radiotherapy, which can ultimately lead to tumor recurrence and metastasis. As a novel type of nano-radiosensitizer, silver nanoparticles (AgNPs) have shown promising radiosensitizing properties in the radiotherapy of glioma, but their ability to efficiently enter and accumulate in tumor cells needs to be improved. In the current study, AS1411 and verapamil (VRP) conjugated bovine serum albumin (BSA) coated AgNPs (AgNPs@BSA-AS-VRP) were synthesized and characterized. Dark-field imaging and inductively coupled plasma mass spectrometry were applied to investigate the accumulation of AgNPs@BSA-AS and AgNPs@BSA-AS-VRP mixed in different ratios in U251 glioma cells. To assess the influences of 19:1 mixed AgNPs@BSA-AS and AgNPs@BSA-AS-VRP on the P-glycoprotein (P-gp) efflux activity, rhodamine 123 accumulation assay was carried out. Colony formation assay and tumor-bearing nude mice model were employed to examine the radiosensitizing potential of 19:1 mixed AgNPs@BSA-AS and AgNPs@BSA-AS-VRP. Thioredoxin Reductase (TrxR) Assay Kit was used to detect the TrxR activity in cells treated with different functionally modified AgNPs. Characterization results revealed that AgNPs@BSA-AS-VRP were successfully constructed. When AgNPs@BSA-AS and AgNPs@BSA-AS-VRP were mixed in a ratio of 19:1, the amount of intracellular nanoparticles increased greatly through AS1411-mediated active targeting and inhibition of P-gp activity. In vitro and in vivo experiments clearly showed that the radiosensitization efficacy of 19:1 mixed AgNPs@BSA-AS and AgNPs@BSA-AS-VRP was much stronger than that of AgNPs@BSA and AgNPs@BSA-AS. It was also found that 19:1 mixed AgNPs@BSA-AS and AgNPs@BSA-AS-VRP significantly inhibited intracellular TrxR activity. These results indicate that 19:1 mixed AgNPs@BSA-AS and AgNPs@BSA-AS-VRP can effectively accumulate in tumor cells and have great potential as high-efficiency nano-radiosensitizers in the radiotherapy of glioma.
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发表时间: 2009-08
期刊: Cell Research
影响因子: 44.1
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影响因子: 4.6
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