Fabrication of epidermal growth factor imprinted and demethylcantharidin loaded dendritic mesoporous silica nanoparticle: An integrated drug vehicle for chemo-/antibody synergistic cancer therapy

Abstract

Currently, administration of antibodies combining with anti-cancer drugs strategies are powerful therapies options for certain cancers, however, the widely use of natural antibodies is still limited by the high cost and the risk of immunogenic reactions. In this study, an epidermal growth factor (EGF)-imprinted and anti-tumor agent demethylcantharidin (DMC) loaded nanoparticle which with ability of both serving as the artificial antibody and delivering DMC to be used for chemotherapy was designed. Polydopamine (PDA) was chosen as the molecular imprinting polymer (MIP) materials and coated into the pore channels of dendritic mesoporous silica nanoparticles (DMSN) which with nano size spherical shape and ultra-large pore size. Finally, DMC was introduced into the DMSN@MIP by coupling with the hydroxyl groups of PDA films. The successfully prepared DMSN@MIP-DMC was with specific EGF adsorption ability and high DMC loading capacity. In vitro and in vivo studies results showed that DMSN@MIP-DMC with affinity to EGF inhibit its binding to receptor epidermal growth factor receptor (EGFR), preventing receptor phosphorylation and further promote apoptosis of 4T1 cells induced by DMC. These results imply that DMSN@MIP-DMC has the potential to both serve as the artificial antibody and drug vehicle for delivering anti-tumor drugs.