pH-responsive mesoporous silica nanoparticles functionalized with folic acid and chitosan for targeted epirubicin delivery: In vitro and in vivo efficacy in breast cancer

Abstract

Mesoporous silica nanoparticles (MSNs) are emerging as a promising delivery system for various chemotherapy drugs due to their safety and compatibility with biological systems. In this study, MSNs functionalized with folic acid (FA) and chitosan (CS) loaded with epirubicin (EPI) were characterized to evaluate the efficacy of these nanoparticles in inhibiting MCF-7cell line and in mice bearing 4 T1 tumor. MSN-EPI@CS-FA showed a high drug loading efficiency of 79.49 %, likely due to the large pore volume and surface functional groups on the MSNs. In both in vitro and in vivo studies, the functionalized MSNs exhibited superior efficacy compared to unmodified MSNs. Notablygene expression results revealed enhanced expression levels of proapoptotic markers (Bax, caspase 3, and caspase 9) and down-regulation of the anti-apoptotic genes (Bcl-2, cyclin D, cyclin E, MMP-2, and MMP-9) in cells treated with MSN-EPI@CS-FA, indicating apoptosis through the mitochondrial pathway. In cells treated with MSN-EPI@CS-FA, there were significant changes in reactive oxygen species (ROS) levels, Malondialdehyde (MDA) content, and antioxidant enzyme activity compared to the MSN-EPI and EPI groups. In a murine 4 T1 breast tumor model, MSN-EPI@CS-FA more strongly than MSN-EPI inhibited tumor growth without drug accumulation in the liver or spleen and substantial targeting of the tumor, highlighting the efficacy of folate receptor-mediated active targeting in improving therapeutic outcomes. Therefore MSN-EPI@CS-FA exhibits significant promise as a potent anticancer therapy.

Keywords: Chitosan; In vitro and in vivo study; Mesoporous silica nanoparticle.