Doxorubicin Hydrochloride-Loaded Mesoporous Silica Nanoparticles Inhibit Non-Small Cell Lung Cancer Metastasis by Suppressing VEGF-Mediated Angiogenesis

Mesoporous silica nanoparticles (MSNs) are widely used nanoparticles with a pore rich structure that is suitable for drug delivery. Here, we used MSNs to carry and deliver doxorubicin hydrochloride (DOX) in vivo to study the features of DOXloaded MSNs (MSNs@DOX). We used TEM and zeta potential to illustrate that MSNs@DOX increase apoptosis and decrease metastasis of tumor cells. We used MTT, flow cytometry, Western blotting, wound healing, and transwell assays, as well as an in vivo metastasis model to explore the anti-carcinoma efficacy of MSNs@DOX. Our results showed that DOX was efficiently loaded into MSNs measuring approximately 88±11 nm, which significantly increased the antitumor efficacy of DOX on lung cancer, both in vitro and in vivo, compared to a regular DOX treatment. MSNs@DOX markedly induced apoptosis through cytochrome C release and the caspase family. Furthermore, cell migration and invasion were sharply inhibited, both in vitro and in vivo. We also found that the enhanced effect of MSNs@DOX might be due to an increased cellular uptake by tumor cells based on the enhanced permeability and retention time of the nanoparticles. Matrigel plug assays and Western blotting assays revealed that the molecular mechanism behind the anti-metastasis effect might be attributed to the suppression of VEGF-mediated angiogenesis. Our results offer a new perspective on the application of nanoparticles against metastasis.