Injectable and Near-Infrared-Responsive Hydrogels Encapsulating Dopamine-Stabilized Gold Nanorods with Long Photothermal Activity Controlled for Tumor Therapy.

Abstract

Gold nanorods (AuNRs) are confirmed to have excellent and repeated photothermal properties under near-infrared (NIR)-light irradiation above 780 nm. However, AuNRs easily leaked out from local pathological tissues and circulated in the body, reducing photothermal therapy (PTT) efficacy. By complexing AuNRs with a scaffold via interactions, AuNRs might be dispersed in the scaffold and fixed in the tumor site. Thus, based on the mussel-mimetic adhesion concept, AuNRs were designed to be coated with polydopamine (PDA), and then the prepared polydopamine-coated AuNRs (AuNR-PDA) were incorporated into a thermosensitive injectable hydrogel composed of β-glycerophosphate-bound chitosan (CGP) and dopamine-modified alginate (Alg-DA) efficiently. Due to the strong interactions between PDA and polymers, AuNR-PDA could be immobilized stably and evenly into the obtained CGP/Alg-DA/AuNR composite hydrogel, which can avoid overheating locally or leaking out. The sol-gel transition temperature of the composite hydrogel was adjusted to the body temperature at around 37 °C to be conveniently injectable in vivo. With NIR irradiation at 808 nm of wavelength, the composite hydrogel was locally heated quickly to over 50 °C depending on controlling the irradiation powers and times. Moreover, the in vitro cytotoxicity test of the composite hydrogel showed good biocompatibility to normal cells but obvious suppression to tumor cells' growth under multiple times of photothermal therapy. Furthermore, the in vivo antitumor test demonstrated the obvious suppression to tumor growth of the CGP/Alg-DA/AuNR composite hydrogel under multiple PTTs. Therefore, the injectable CGP/Alg-DA/AuNR hydrogel could be a promising candidate for the long-term repeated photothermal treatment of tumors.