Cisplatin and si-Notch 1-Folic Acid-Conjugated Mesoporous Silica Nanoparticles Prevent Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is still a severe disorder with a high mortality and new effective therapies are urgently required. Our study aimed to explore the effect of combined cisplatin with conjugated mesoporous silica nanoparticles (MSN) on HCC. We prepared copolymer PCL-b-PPEEA and PEG-b-PCL-Pt(IV) to load drugs, while Pt(IV) MNP/siRNA nanoparticles were synthesized. The nanoparticles were characterized by transmission electron microscopy and Western blot analysis. Flow cytometry was determined to detect apoptosis of CD133 + SMMC7721 cells. Then cells were treated with Pt(IV) MNP/siRNA, MNP/siRNA or PBS, where the Notch1 and related gene expression were determined by RT-qPCR with clone formation detected by agarose assay. The synthesized nanoparticles were about 90 nm and absorbed by cancer cells with a high stability. Compared with the cisplatin, Pt(IV) MNP/siNotch1 nanoparticles exhibited enhanced cytotoxicity and downregu-lated expression of cisplatin-induced Notch1 and cancer stem cells. Moreover, the MNP/siNotch1 nanoparticles significantly suppressed the proliferation and clonal formation of CD133 + SMMC7721 cells. Co-delivery of cisplatin, si-Notch1 and folic acid conjugated MSN can inhibit the development of HCC, indicating that it might be a novel treatment approach for HCC in the future.