载阿霉素介孔二氧化硅纳米药物对膀胱癌的抑制作用

苏巧玲; 邱和平; 李金瑾; 黄垣堤; 方强; 支轶; 李为兵

doi:10.16016/j.1000-5404.202106173

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载阿霉素介孔二氧化硅纳米药物对膀胱癌的抑制作用

专题报道：膀胱癌基础与临床研究 | 更新时间：2026-01-09

- 载阿霉素介孔二氧化硅纳米药物对膀胱癌的抑制作用
- Inhibitory effect of doxorubicin-loaded mesoporous silica nanoparticles on bladder cancer cells
- 第三军医大学学报 2021年43卷第23期页码：2562-2569
- 作者机构：
  
  401120 重庆，重庆医科大学附属第三医院泌尿外科
- 作者简介：
  
  [李为兵，E-mail: liweibing63@cqmu.edu.cn LI Weibing, E-mail: liweibing63@cqmu.edu.cn
- 基金信息：
  
  重庆医科大学附属第三医院科研孵化项目(KY08026);2021年渝北区科技计划项目(2021(农社)38)
- DOI：10.16016/j.1000-5404.202106173
  中图分类号： R737.14;R965;R979.14
- 收稿：2021-06-22，
  
  修回：2021-09-29，
  
  纸质出版：2021-12-15
- 稿件说明：
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苏巧玲, 邱和平, 李金瑾, 等. 载阿霉素介孔二氧化硅纳米药物对膀胱癌的抑制作用[J]. 第三军医大学学报, 2021,43(23):2562-2569.

Qiaoling SU, Heping QIU, Jinjin LI, et al. Inhibitory effect of doxorubicin-loaded mesoporous silica nanoparticles on bladder cancer cells[J]. Journal of Third Military Medical University, 2021, 43(23): 2562-2569.
苏巧玲, 邱和平, 李金瑾, 等. 载阿霉素介孔二氧化硅纳米药物对膀胱癌的抑制作用[J]. 第三军医大学学报, 2021,43(23):2562-2569. DOI： 10.16016/j.1000-5404.202106173.

Qiaoling SU, Heping QIU, Jinjin LI, et al. Inhibitory effect of doxorubicin-loaded mesoporous silica nanoparticles on bladder cancer cells[J]. Journal of Third Military Medical University, 2021, 43(23): 2562-2569. DOI： 10.16016/j.1000-5404.202106173.

摘要

目的

制备一种包载阿霉素(doxorubicin，DOX)的介孔二氧化硅纳米粒子(mesoporous silica nanoparticles，MSN)，评价其物理性质、药物释放能力、肿瘤细胞摄取、细胞增殖抑制效果及凋亡作用。

方法

采用浸润法将DOX负载到MSN的孔道中以制备介孔二氧化硅纳米药物(MSN-DOX)，通过透射电镜观察纳米药物形貌，纳米粒径电位分析仪测量其大小和表面电荷。利用透析法观察纳米药物在不同pH值(5.5、6.8、8.0)条件下的药物释放行为。采用激光共聚焦显微镜观察膀胱癌细胞对纳米药物的摄取情况。通过CCK-8检测MSN的生物相容性以及纳米药物的细胞增殖抑制效果。通过检测凋亡相关蛋白的表达水平分析纳米药物对膀胱癌细胞的凋亡作用。

结果

制备的纳米药物MSN-DOX呈球形，大小均匀，粒径为(203.6±3.0) nm，表面电荷为(-8.1±4.7) mV，DOX载药量为4.83%，包封率为10.15%。体外药物释放结果显示纳米药物缓慢释放DOX，其释放速度和总释放量与环境pH值相关，环境pH值越低，药物释放速度越快，总释放量越多。激光共聚焦显微镜观察结果显示纳米药物可以被肿瘤细胞高效摄取，从而增加药物在细胞内的蓄积。CCK-8检测表明MSN生物相容性好，纳米药物肿瘤增殖抑制效果显著。凋亡相关蛋白检测显示纳米药物增加细胞凋亡蛋白的表达，促进肿瘤细胞凋亡。

结论

制备的介孔二氧化硅纳米药物性能优良、结构稳定，可以被膀胱癌细胞高效摄取，有效抑制肿瘤细胞增殖并促进肿瘤细胞凋亡。

Abstract

Objective

To prepare mesoporous silica nanoparticles (MSN) loaded with doxorubicin (DOX) and to evaluate their physical properties

drug release

uptake by tumor cells

inhibition of cell proliferation and promotion of apoptosis.

Methods

DOX was loaded into the channels of MSN by infiltration to prepare mesoporous silica nanocomposites (MSN-DOX)

whose morphology was then observed using transmission electron microscopy (TEM)

and the size and surface charge of nanocomposites were measured with a nano particle size analyzer. Dialysis bag was applied to study drug release behavior of the nanocomposites under different pH conditions. Laser confocal microscopy was used to observe the uptake of MSN-DOX by bladder cancer cells. CCK-8 assay was carried out to detect the biocompatibility of MSN and the inhibitory effect of MSN-DOX on cell proliferation. Finally

the expression of apoptosis-related proteins was tested to analyze the effect of MSN-DOX on apoptosis.

Results

The prepared nanocomposites were spherical

uniform in size

in a size of 203.6±3.0 nm

with a surface charge of -8.1±4.7 mV. The DOX loading was 4.83%

and the encapsulation efficiency was 10.15%.

In vitro

studies showed that DOX was slowly released from the nanocomposites

and the release rate and total release amount were correlated with the environmental pH value. Lower pH value led

to faster drug release rate and more total release amount. Cellular uptake experiments indicated the nanocomposites were efficiently ingested by tumor cells

thereby increasing the intracellular drug accumulation. In addition

MSN had good biocompatibility

and MSN-DOX significantly inhibited the proliferation and promoted the apoptosis of tumor cells

with increased expression levels of apoptosis-related proteins.

Conclusion

Our prepared MSN-DOX nanocomposites have good properties and stable structure

which can be efficiently ingested by bladder cancer cells

thus effectively inhibiting proliferation and promoting apoptosis of tumor cells.

关键词

Keywords

references

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