Photothermally Modulated Intracellular Delivery of Therapeutic Proteins Using Gold-Collagen Hybrid Nanoparticles

Stimuli-responsive nanoparticles have attracted considerable attention as nanocarriers for the intact intracellular delivery of active biotherapeutics with high stability and controllability. In this study, we developed light- and heat-responsive gold-collagen hydrogel nanoparticles (Au-CHPs) for the intracellular delivery of therapeutic proteins. Au-CHPs composed of collagen, thermosensitive polymers, and gold nanoparticles were fabricated by the simultaneous reduction of gold ions during radical polymerization. Under resonant light, Au-CHPs induce proximate environmental changes by immediately increasing the local temperature. Three proteins, fibroblast growth factor, superoxide dismutase, and epidermal growth factor, with different cellular functions were electrostatically incorporated into the Au-CHPs with a high loading efficiency of over 57%. Photothermal triggering through Au-CHPs boosted wound healing, reactive oxygen species scavenging, and cellular spheroid growth, owing to the on-demand release and rapid diffusion of proteins. We envision that stimuli-responsive hybrid materials for carrying bioactive proteins will help with the development of controlled delivery systems for biomedical and cosmeceutical applications.