Chlorin e6 and polydopamine modified gold nanoflowers for combined photothermal and photodynamic therapy

Abstract

Combinational photo-based approaches with enhanced efficacy for cancer therapy have garnered increasing attention in recent years. In this work, a multifunctional system for synergistic photothermal and photodynamic cancer therapy was successfully prepared. The system consists of gold nanoflowers (AuNFs) conjugated with Chlorin e6 (Ce6), and then coated with a polydopamine (PDA) layer. AuNFs with diameters around 80 nm and a broad absorbance in the visible–near infrared (Vis–NIR) range of 500 to 800 nm, were successfully synthesized by a two-step process at 0 °C, using HAuCl₄, ascorbic acid (AA), and hydroxylamine hydrochloride (NH₂OH·HCl) as the reactants. Glutathione (GSH) molecules chemically anchored to the gold surfaces were used to provide addressable sites for Ce6 conjugated to GSH-AuNFs through an amidation reaction. A PDA layer was then wrapped outside the Ce6-GSH-AuNFs via self-polymerization of dopamine, which provided additional chemical modification and functionalization. Finally, the multifunctional PDA-Ce6-GSH-AuNFs were obtained. The content of Ce6 incorporated into the AuNFs was 14.0 wt%, and the singlet oxygen yield of PDA-Ce6-GSH-AuNFs was approximately 91.0% of that of free Ce6. PDA-Ce6-GSH-AuNFs showed better photothermal conversion efficiency (η = 23.6%), lower cytotoxicity, and faster cell internalization. Both in vitro and in vivo investigation of the combined treatment with a near-infrared (NIR) laser (660 nm for photodynamic therapy, and 808 nm for photothermal therapy) demonstrated that PDA-Ce6-GSH-AuNFs had excellent phototoxicity and synergistic effects of killing cancer cells. Hence, PDA-Ce6-GSH-AuNFs are a dual phototherapeutic agent that exhibits photodynamic and photothermal therapeutic effects and has potential application in enhanced cancer therapy.