Potential Applications of ROS-Responsive Silk Fibroin Materials in Smart Drug Delivery Systems

Silk fibroin (SF) is a promising drug carrier because of its unique macromolecular structure and excellent biocompatibility and biodegradability. In this study, we developed a responsive SF material by introducing reactive oxygen species (ROS)-cleavable thioketal (TK) between the SF macromolecular chains. TK was synthesized with carboxyl (−COOH) groups at both ends of the molecules, and its C–S bonds could be cleaved in an ROS-rich environment. The molecular weight and chemical structure of TK were identified using mass spectrometry and 1 H-nuclear magnetic resonance. Subsequently, we prepared SF/TK films and found that KO 2 treatment resulted in a significant change in their morphology and mechanical properties relative to unmodified SF films when the SF/TK mass ratios ranged from 100:3 to 100:5. Based on these findings, a camptothecin (CPT)-loaded SF/TK drug carrier was developed at an SF/TK mass ratio of 100:3 by self-assembly. Release kinetics demonstrated that the release rate of CPT from SF/TK nanoparticles was 2.5 times higher than that from SF microspheres in the KO 2 environment. There were distinct changes in the surface morphologies of the nanoparticles. This study suggests that introducing TK can confer ROS-responsive cleavage on SF materials, which have potential applications for smart drug delivery systems.