Synthesis and characterization of Fe3O4-PEG-LAC-chitosan-PEI nanoparticle as a survivin siRNA delivery system
Synthesis and characterization of Fe3O4-PEG-LAC-chitosan-PEI nanoparticle as a survivin siRNA delivery system
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DOI：
10.1177/0960327116646618
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发表时间：
2017-03-01
影响因子：
2.8
通讯作者：
Entezami, A. A.
中科院分区：
文献类型：
--
作者：
Arami, S.;Rashidi, M. R.;Entezami, A. A.
传统的肿瘤治疗方法的局限性促使研究者寻找新的安全有效的治疗策略。这些策略之一是使用小干扰RNA（siRNA）。这里的一个主要挑战是siRNA递送到细胞中。本研究的目的是设计和制备一种生物相容性、生物可降解性和安全性的纳米颗粒，用于将siRNA递送到人乳腺癌MCF-7和白血病K562细胞中。以聚乙二醇-乳酸共聚物（PEG-LAC）、壳聚糖和聚乙烯亚胺（PEI）为载体，制备了磁性纳米粒子。通过傅里叶变换红外光谱和zeta电位对纳米粒子进行了表征。在凝胶阻滞试验中，Fe 3 O 4-PEG-LAC-chitosan-PEI纳米粒显示出有效且稳定的Survivin siRNA负载。采用3-（4，5-二甲基-2-噻唑基）-2，5-二苯基-2H-溴化四氮唑法检测纳米粒的细胞毒性，并与MTX和siRNA联合应用的细胞毒性进行比较，以评价MTX和survivin siRNA可能的协同作用。具有和不具有非互补siRNA的纳米颗粒显示出对两种细胞系的低毒性;然而，观察到MTX添加到用纳米颗粒本身或与非互补siRNA复合处理的MCF-7细胞后细胞存活百分比降低两倍。虽然生存素siRNA纳米复合物导致细胞存活百分比降低三倍，但其与MTX的组合并未导致细胞毒性效应显著增加。因此，Fe 3 O 4-PEG-LAC-chitosan-PEI纳米粒可作为一种潜在的载体，用于增强survivin siRNA在MCF-7和K562细胞中的表达。
The limited effectiveness of the conventional methods for cancer treatment makes the researchers to find novel safe and effective therapeutic strategies. One of these strategies is to use small interfering RNAs (siRNAs). A major challenge here is the siRNA delivery into the cells. The purpose of this study was to design and prepare a biocompatible, biodegradable, and safe nanosized particle for siRNA delivery into human breast cancer MCF-7 and leukemia K562 cells. Chemically synthesized magnetic nanoparticles containing polyethyleneglycol-lactate polymer (PEG-LAC), chitosan, and polyethyleneimine (PEI) were successfully prepared and used as a gene delivery vehicle. The nanoparticles were characterized by Fourier transform infrared spectroscopy and zeta potential. The Fe3O4-PEG-LAC-chitosan-PEI nanoparticle showed efficient and stable survivin siRNA loading in gel retardation assay. The cytotoxicity of the prepared nanoparticle was studied using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and was compared with that of mitoxantrone (MTX) in combination with the prepared siRNA delivery system to evaluate the possible synergic effect of MTX and survivin siRNA. The nanoparticles with and without noncomplementary siRNA showed low toxicity against both cell lines; however, a twofold decrease was observed in cell survival percent after MTX addition to MCF-7 cells treated with either nanoparticle itself or complexed with noncomplementary siRNA. While survivin siRNA nanoplex caused threefold decrease in the cell survival percent, its combination with MTX did not result in a significant increase in the cytotoxic effect. Therefore, Fe3O4-PEG-LAC-chitosan-PEI nanoparticle should be considered as a potential carrier for enhanced survivin siRNA delivery into MCF-7 and K562 cells.