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