Intracellular Biodegradation of Ag Nanoparticles, Storage in Ferritin, and Protection by a Au Shell for Enhanced Photothermal Therapy

Despite their highly efficient plasmonic properties, gold nanoparticles are currently preferred to silver nanoparticles for biomedical applications such as photothermal therapy due to their high chemical stability in the biological environment. To confer protection while preserving their plasmonic properties, we allied the advantages of both materials and produced hybrid nanoparticles made of an anisotropic silver nanoplate core coated with a frame of gold. The efficiency of these hybrid nanoparticles (Ag@AuNPs) in photothermia was compared to monometallic silver nanoplates (AgNPs) or gold nanostars (AuNPs). The structural and functional properties of AuNPs, AgNPs, and Ag@AuNPs were investigated in environments of increasing complexity, in water suspensions, in cells, and in tumors in vivo. While AgNPs showed the greatest heating efficiency in suspension (followed by Ag@AuNPs and AuNPs), this trend was reversed intracellularly within a tissue-mimetic model. In this setup, AgNPs failed to provide consistent photothermal conversion over time, due to structural damage induced by the intracellular environment. Remarkably, the degraded Ag was found to be stored within the iron-storage ferritin protein. By contrast, the Au shell provided the Ag@AuNPs with total Ag biopersistence. As a result, photothermal therapy was successful with Ag@AuNPs in vivo in a mouse tumor model, providing the ultimate proof on Au shell's capability to shield the Ag core from the harsh biological environment and preserve its excellent heating properties.