Radiofrequency-responsive dual-valent gold nanoclusters for enhancing synergistic therapy of tumor ablation and artery embolization

Abstract Interventional cancer therapy, till date, experiences a major challenge to improve the synergistic effect of radiofrequency ablation (RFA) and trans-artery embolization (TAE). Here, RF-responsive dual-valent gold nanoclusters (dvGC@PNAs), as multifunctional blood-vessel-embolic agents, have been successfully manufactured for comprehensive interventional theranostics of solid tumors. Distinct RF-induced heating effect was obtained by reducing Au(I)-thiolate complex using l -glutathione under the template polymer of temperature-sensitive poly(N-isopropylamide-co-acrylic acid) (PNAs), the well-defined dvGC@PNAs with the core-shell nanostructure of Au(0) atoms surrounded by a high content of Au(I) ions, thereby triggering cell apoptosis, necrosis, and metastasis inhibition. Efficient TAE cancer therapy can also be achieved by rapid diffusion of dvGC@PNAs into tumor peripheral arteries that impede tumor blood supply by their favorable temperature-sensitive sol-gel transition. The immunofluorescent analyses substantiated the greatly improved tumor microenvironment post TAE procedure, owing to the radiofrequency-responsive dvGC@PNAs, induced a favorable immune response, thereby augmenting the synergistic antitumor effect of RFA and TAE. The present study provides a valuable paradigm for ameliorating the synergistic interventional therapies by the rational design of RF-responsive metal nanoclusters.