The major limitation of any cancer therapy lies in the difficulty of precisely controlling the localization of the drug in the tumor cells. To improve this drawback, our study explores the use of actively-targeted chemo-photo-nanocarriers that recognize and bind to epidermal growth factor receptor-overexpressing cells and promote the local on-demand release of the chemotherapeutic agent doxorubicin triggered by light. Our results show that the attachment of high concentrations of doxorubicin to cetuximab-IRDye700DX-mesoporous silica nanoparticles yields efficient and selective photokilling of EGFR-expressing cells mainly through singlet oxygen-induced release of the doxorubicin from the nanocarrier and without any dark toxicity. Therefore, this novel triply functionalized nanosystem is an effective and safe nanodevice for light-triggered on-demand doxorubicin release.
Keywords: EGFR; cetuximab; chemotherapy; drug delivery; mesoporous silica nanoparticles; photodynamic therapy; singlet oxygen.