Preparation and characterization of doxorubicin and siRNA co-loaded CLMSNs and study on anti-multidrug-resistant tumor cells

ZHANG Mengwei; YANG Shuoye; YANG Yanan; WANG Zhenwei; QU Lingbo

doi:10.6039/j.issn.1001-0408.2022.23.12

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Preparation and characterization of doxorubicin and siRNA co-loaded CLMSNs and study on anti-multidrug-resistant tumor cells

更新时间：2023-02-22

- Preparation and characterization of doxorubicin and siRNA co-loaded CLMSNs and study on anti-multidrug-resistant tumor cells
- ZHONGGUO YAOFANG Vol. 33, Issue 23, Pages: 2880-2885(2022)
- 作者机构：
  
  1.河南工业大学生物工程学院，郑州　450001
  2.郑州市生物医药功能分子重点实验室，郑州　450001
  3.郑州大学化学与分子工程学院，郑州　450001
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2022.23.12
  CLC： R944.9;R979.1
- Published：15 December 2022，
  
  Received：11 June 2022，
  
  Revised：17 October 2022，
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张梦玮,杨硕晔,杨亚南等.共载阿霉素与小干扰RNA的脂质介孔硅纳米粒的制备表征及抗多药耐药肿瘤细胞研究 ^Δ[J].中国药房,2022,33(23):2880-2885.

ZHANG Mengwei,YANG Shuoye,YANG Yanan,et al.Preparation and characterization of doxorubicin and siRNA co-loaded CLMSNs and study on anti-multidrug-resistant tumor cells[J].ZHONGGUO YAOFANG,2022,33(23):2880-2885.
张梦玮,杨硕晔,杨亚南等.共载阿霉素与小干扰RNA的脂质介孔硅纳米粒的制备表征及抗多药耐药肿瘤细胞研究 ^Δ[J].中国药房,2022,33(23):2880-2885. DOI： 10.6039/j.issn.1001-0408.2022.23.12.

ZHANG Mengwei,YANG Shuoye,YANG Yanan,et al.Preparation and characterization of doxorubicin and siRNA co-loaded CLMSNs and study on anti-multidrug-resistant tumor cells[J].ZHONGGUO YAOFANG,2022,33(23):2880-2885. DOI： 10.6039/j.issn.1001-0408.2022.23.12.

摘要

目的

制备共载阿霉素（DOX）与小干扰RNA（siRNA）的脂质介孔硅纳米粒（CLMSNs-SS-NH

@DOX/siRNA），并对其进行表征及抗多药耐药肿瘤细胞研究。

方法

先以介孔硅纳米粒（MSNs）为基础制备MSNs-SS-NH

@DOX，并以阳离子脂质体（CLs）对其包覆制得CLMSNs-SS-NH

@DOX，进一步负载siRNA即得CLMSNs-SS-NH

@DOX/siRNA。测定该制剂粒径及Zeta电位，观察其微观形态并进行差示扫描量热分析、X射线衍射分析、红外光谱分析、物理吸附分析；测定该制剂在不同pH条件下（pH5.0、pH7.4）及不同谷胱甘肽浓度下（0、2、5、10 mmol/L）DOX的体外释放度；考察该制剂对耐DOX型乳腺癌细胞MCF-7/ADR摄取、迁移、凋亡、周期及P-糖蛋白（P-gp）表达的影响。

结果

CLMSNs-SS-NH

@DOX/siRNA结构清晰，表面脂膜层明显，粒径为（197.63±3.75）nm，Zeta电位为（20.64±0.98）mV，理化性质良好。体外释放结果显示，CLMSNs-SS-NH

@DOX/siRNA具有良好的pH/还原双重响应释药特性。细胞实验结果显示，经CLMSNs-SS-NH

@DOX/siRNA干预后，MCF-7/ADR细胞的药物摄取显著增强，迁移率和P-gp表达水平均显著降低，总凋亡比例和G

期所占比例均显著升高（

＜0.05）。

结论

本研究成功制备同时负载DOX和siRNA 的CLMSNs-SS-NH

@DOX/siRNA；该制剂理化性质良好，具有pH/还原双重响应释药特性，且可通过下调P-gp表达逆转 MCF-7/ADR细胞多药耐药。

Abstract

OBJECTIVE

To prepare lipid-coated mesoporous silica nanoparticles （CLMSNs） co-loaded with doxorubicin （DOX） and siRNA （CLMSNs-SS-NH

@DOX/siRNA），and to characterize it and study anti-multidrug-resistant tumor cells.

METHODS

MSNs-SS-NH

@DOX was prepared on the basis of mesoporous silica （MSNs），covered with cationic liposomes （CLs） to synthesize CLMSNs-SS-NH

@DOX，and then obtain CLMSNs-SS-NH

@DOX/siRNA by co-loading with siRNA. The particle size and Zeta potential of the preparation were determined，and its micromorphology was observed； differential scanning calorimetry，X-ray diffraction，infrared spectroscopy and physical adsorption analysis were conducted. The

in vitro

release of DOX from the preparation was determined under different pH conditions （pH5.0，pH7.4） and different glutathione concentrations （0，2，5，10 mmol/L）. The effects of this preparation on the uptake，migration，apoptosis，cycle and P-glycoprotein （P-gp） expression of MCF-7/ADR in DOX-resistant breast cancer cells were investigated.

RESULTS

CLMSNs-SS-NH

@DOX/siRNA had a clear core-shell structure，obvious lipid membrane layer，particle size of （197.63±3.75） nm，Zeta potential of （20.64±0.98） mV，and with good physical and chemical properties.

In vitro

release results showed that CLMSNs-SS-NH

@DOX/siRNA possessed good pH/reduction double-response. The results of cell experiment showed that after intervened with CLMSNs-SS-NH

@DOX/siRNA，the fluorescence intensity of MCF-7/ADR cells was significantly enhanced，the migration rate and P-gp expression level were significantly reduced，while total proportion of apoptosis and that of G

phase were significantly increased （

＜0.05）.

CONCLUSIONS

In this study，DOX and siRNA co-loaded CLMSNs-SS-NH

@DOX/siRNA is prepared successfully， which has good physical and chemical properties， pH/reduction double-response properties. It can reverse the multidrug resistance of MCF-7/ADR cells by down-regulation of P-gp expression.

关键词

介孔硅小干扰RNA阿霉素抗肿瘤多药耐药

Keywords

siRNAdoxorubicinanti-tumormultidrug resistance

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