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Indexed by:期刊论文

Date of Publication:2017-12-20

Journal:INTERNATIONAL JOURNAL OF PHARMACEUTICS

Included Journals:Scopus、SCIE、PubMed

Volume:534

Issue:1-2

Page Number:71-80

ISSN No.:0378-5173

Key Words:ADH-1; Hyaluronic acid; Mesoporous silica nanoparticles; Drug delivery; Invasion and metastasis

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/NH2) 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.