Hyaluronic Acid-Modified Au–Ag Alloy Nanoparticles for Radiation/Nanozyme/Ag+ Multimodal Synergistically Enhanced Cancer Therapy

Gold nanoparticles (AuNPs) have been widely documented as tumor radiosensitizers via enhanced energy deposition of ionizing radiation. However, the sensitization efficiency of AuNPs is still far from satisfactory owing to the irradiation on nontarget tissues and the tumor radio-resistance. To address these issues, we report herein the rational design and development of hyaluronic acid-modified Au-Ag alloy nanoparticles (Au-Ag@HA NPs) with effective tumor radiosensitization by receptor mediated tumor targeting as well as microenvironment-activated hydroxyl radicals (•OH) generation. In our work, Au-Ag@HA NPs were synthesized by the coreduction of HAuCl₄ and AgNO₃ in the presence of trisodium citrate, followed by surface modification of HA to the Au-Ag alloy NPs. HA modification affords the alloy NPs with specific targeting to 4T1 breast cancer cells overexpressing CD44 receptor, while the introduction of Ag atom imparts the alloy NPs with superior multienzyme-like activities to the monometallic AuNPs for efficient tumor catalytic therapy. More importantly, the ionizing radiation and peroxidase-like activity of Au-Ag@HA NPs boost the production of •OH and the release of toxic Ag⁺ in the tumor sites, thereby leading to effective tumor therapeutic outcome. This work provides a promising treatment paradigm for radiation/nanozyme/Ag⁺ combined therapy against cancer and will advance the design and development of multifunctional nanoplatforms for synergetically enhanced tumor therapy.