Supercritical Fluid-Assisted Fabrication of Indocyanine Green-Encapsulated Silk Fibroin Nanoparticles for Dual-Triggered Cancer Therapy.

Despite the success and advantages over traditional chemotherapeutic strategies, photothermal therapy (PTT) suffers from certain limitations, such as poor stability, low therapeutic efficacy of PTT agents in vivo, and their affinity loss during the multistep synthesis process of delivery carriers, among others. To address these limitations, we designed a stable, biocompatible, and dual-triggered formulation of indocyanine green (ICG)-encapsulated silk fibroin (SF) (ICG-SF) nanoparticles using supercritical fluid (SCF) technology. We demonstrated that ICG encapsulation in SF through this environmental-friendly approach has offered excellent photothermal stability, the pH-responsive release of ICG from SF specifically in the tumor acidic environment, and its substantial activation with near-infrared (NIR) light at 808 nm significantly enhanced the PTT efficiency. In vitro and in vivo photothermal experiments have shown that these ICG-SF nanoparticles were capable of devastating tumor cells merely under light-induced hyperthermia. Together, these results have suggested that the biocompatible ICG-SF nanoparticles prepared by the SCF process resulted in high PTT efficiency and may have a great potential as a delivery system for sustained cancer therapy.