Gold nanorods coated with self-assembled silk fibroin for improving their biocompatibility and facilitating targeted photothermal–photodynamic cancer therapy

Gold nanorods (AuNRs) have shown great potential as photothermal agents for cancer therapy. However, the biosafety of AuNRs ordinarily synthesized using a cationic ligand assistance procedure has always been a subject of controversy, which limits their application in tumor therapy. In this study, we propose a novel strategy to enhance the biocompatibility of AuNRs by constructing a biological coating derived from silk fibroin (SF) on their surface. The SF coating could be easily and precisely manipulated using a layer-by-layer (LBL) assembly method. The resulting SF-coated gold nanorods (AuNRs@SF) exhibited reduced cytotoxicity and improved hemocompatibility compared to untreated AuNRs. Moreover, the treated nanorods were easily modified with a tumor-targeting peptide (AuNRs@MTSF) and efficiently loaded indocyanine green (ICG). Both <i>in vitro</i> and <i>in vivo</i> analyses demonstrated that AuNRs@MTSF could more effectively reach tumor tissue and enter MCF-7 cells. Furthermore, after loading ICG, AuNRs@MTSF exhibited superior antitumor efficacy compared to other groups by combining photodynamic therapy (PDT) with photothermal therapy (PTT) under near-infrared (NIR) irradiation without inducing any side effects. This work suggests that SF coating of gold nanorods is a potential approach for improving their biocompatibility, and that function-modified AuNRs@SF are effective nanoplatforms for targeted and multimodal tumor therapy.