Vanadium nitride quantum dots-based nanozyme in synergy with immune checkpoint blockade for enhanced cancer immunotherapy through vanadate and nitric oxide

Advancements in nanobiotechnology have significantly augmented the efficacy of metallodrugs for cancer therapy. Additionally, gas therapies, including oxygen and nitric oxide, hold promise for tumor treatment due to their capacity to manipulate the tumor microenvironment (TME). Herein, we synthesized vanadium nitride (V 2 N) nanosheets (NSs) and converted them into quantum dots (QDs) via hydrothermal synthesis method. After modification with triphenylphosphine (TPP) and soybean phospholipids (SP), the V 2 N@TPP/SP QDs exhibited nanozyme-like activity and activated H 2 O 2 through nonradical pathways, demonstrating effective mitochondria-targeting capabilities. Upon degradation into vanadate, they inhibited Na + /K + ATPase and K + efflux, disrupting mitochondrial membrane potential, and triggering reactive oxygen species (ROS) induced ferroptosis. Furthermore, V 2 N@TPP/SP QDs served as nitric oxide (NO) gas donors, activating reactive nitrogen species (RNS) and enhancing immunogenic cell death (ICD) induction. Combined with α-PD-L1 immunotherapy, they synergistically augmented antitumor treatment by reversing immune suppression in the TME, thereby restraining tumor growth. Our research established a foundation for employing vanadium-based drugs and gas therapy in cancer treatment.