Anti-EGFR antibody conjugated thiol chitosan-layered gold nanoshells for dual-modal imaging-guided cancer combination therapy

Abstract

Developing a novel multifunctional theranostic agent for cancer combination therapy has attracted tremendous attention in recent years. In this report, we designed and developed a new multifunctional nanocarrier based on anti-epidermal growth factor receptor antibody-conjugated and paclitaxel loaded-thiol chitosan-layered gold nanoshells (anti-EGFR-PTX-TCS-GNSs) as a theranostic agent for the first time used for fluorescence/photoacoustic dual-modal imaging-guided chemophotothermal synergistic therapy. The resulting anti-EGFR-PTX-TCS-GNSs showed excellent biosafety, biocompatibility, broad near-infrared (NIR) absorbance, photostability, fast and laser irradiation-controllable drug release, and higher targeting efficiency for efficient chemophotothermal combination therapy of cancer under the guidance of photoacoustic imaging (PAI). The combination therapy was investigated in vitro and in vivo, displaying a powerful anticancer efficiency. More importantly, an in vivo experiment of anti-EGFR-PTX-TCS-GNSs with laser irradiation showed heavy damage to the tumor tissue, killing the tumor cells almost completely. Anti-EGFR-PTX-TCS-GNSs also showed a powerful capacity to visualize tumors, and therefore it is considered a new PAI contrast agent for subsequent therapy. Histological analysis and TUNEL assay further showed much more apoptotic cells, confirming the value of anti-EGFR-PTX-TCS-GNSs. Our results provide a new concept and a promising strategy to develop a novel multifunctional nanotheranostic agent for future clinical applications in diagnosis and therapy.