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双重靶向介孔硅纳米粒子抑制肿瘤细胞侵袭和转移。

Dual targeting mesoporous silica nanoparticles for inhibiting tumour cell invasion and metastasis.

机构信息

School of Life Science and Medicine, Dalian University of Technology, Panjin, Liaoning 124221, China.

School of Life Science and Medicine, Dalian University of Technology, Panjin, Liaoning 124221, China.

出版信息

Int J Pharm. 2017 Dec 20;534(1-2):71-80. doi: 10.1016/j.ijpharm.2017.09.066. Epub 2017 Sep 25.


DOI:10.1016/j.ijpharm.2017.09.066
PMID:28958879
Abstract

The invasion and metastasis of tumour cells are closely correlated with poor prognosis of cancer patients. In this study, a CD44 and N-cadherin dual targeting drug delivery system based on mesoporous silica nanoparticles (MSNs) has been successfully constructed for inhibiting tumour cell invasion and metastasis. Amino modified MSN (MSN/NH) was first synthesized and then functionalized with hyaluronic acid (HA) and ADH-1, constructing the carrier ADH-1-HA-MSN. Doxorubicin hydrochloride (DOX) was selected as a model anticancer drug. The prepared vector had a spherical shape with a narrow distribution of particle size. Flow cytometry and confocal microscopy studies showed that the modification with HA significantly enhanced CD44-mediated cellular uptake of this nanocarrier. ADH-1-HA-MSN/DOX exhibited higher cytotoxicity compared to non-ADH-1 modified counterparts. Of note, a transwell chamber assay demonstrated that the migration and invasion of tumour cells were markedly inhibited by ADH-1-HA-MSN/DOX. Furthermore, Western blotting analysis revealed that ADH-1-HA-MSN/DOX inhibited tumour cell invasion and metastasis by down-regulating N-cadherin expression. Taken together, these results indicated that ADH-1-HA-MSN might be a promising targeted drug delivery system for inhibiting cancer invasion and metastasis.

摘要

肿瘤细胞的侵袭和转移与癌症患者的预后不良密切相关。在本研究中,成功构建了一种基于介孔硅纳米粒子(MSNs)的 CD44 和 N-钙黏蛋白双重靶向药物传递系统,以抑制肿瘤细胞的侵袭和转移。首先合成了氨基修饰的 MSN(MSN/NH),然后用透明质酸(HA)和 ADH-1 对其进行功能化,构建了载体 ADH-1-HA-MSN。盐酸阿霉素(DOX)被选为模型抗癌药物。所制备的载体呈球形,粒径分布较窄。流式细胞术和共聚焦显微镜研究表明,HA 的修饰显著增强了该纳米载体的 CD44 介导的细胞摄取。ADH-1-HA-MSN/DOX 与非 ADH-1 修饰的对照相比具有更高的细胞毒性。值得注意的是,Transwell 室测定表明 ADH-1-HA-MSN/DOX 通过下调 N-钙黏蛋白表达显著抑制肿瘤细胞的迁移和侵袭。此外,Western blot 分析表明,ADH-1-HA-MSN/DOX 通过下调 N-钙黏蛋白表达抑制肿瘤细胞侵袭和转移。综上所述,这些结果表明 ADH-1-HA-MSN 可能是一种有前途的抑制癌症侵袭和转移的靶向药物传递系统。

相似文献

[1]
Dual targeting mesoporous silica nanoparticles for inhibiting tumour cell invasion and metastasis.

Int J Pharm. 2017-9-25

[2]
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[3]
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[7]
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引用本文的文献

[1]
Hyaluronic Acid-Based Nanomaterials Applied to Cancer: Where Are We Now?

Pharmaceutics. 2022-9-30

[2]
The emergence of nanoporous materials in lung cancer therapy.

Sci Technol Adv Mater. 2022-7-20

[3]
Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment.

Cancers (Basel). 2019-12-19

[4]
Antioxidant Nanomaterial Based on Core⁻Shell Silica Nanospheres with Surface-Bound Caffeic Acid: A Promising Vehicle for Oxidation-Sensitive Drugs.

Nanomaterials (Basel). 2019-2-6

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