Atomic vacancies-engineered ultrathin trimetallic nanozyme with anti-inflammation and antitumor performances for intestinal disease treatment

Colitis-associated colorectal cancer, which represents a highly aggressive subtypes of colorectal cancer, requires concurrent antitumor and anti-inflammation therapies in clinic. Herein, we successfully engineered Ru38Pd34Ni28 ultrathin trimetallic nanosheets (TMNSs) by introducing diverse transition metal atoms into the structure of RuPd nanosheets. Density functional theory (DFT) calculations reveal that the elaborate introduction of transition metal Ru and Ni facilitates the formation of Ru–O and Ni–O bonds on the surface of TMNSs for efficient reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging, respectively. Moreover, the engineered abundant atomic vacancies on their surface conspicuously improve the performance in eliminating reactive oxygen and nitrogen species (RONS). The designed TMNSs act as a multi-metallic nanocatalyst with RONS elimination performance for chronic colitis treatment by relieving inflammation, as well as photothermal conversion capability for colon cancer therapy by inducing hyperthermia effect. Profiting from the excellent RONS scavenging activities, TMNSs can down-regulate the expression levels of the pro-inflammatory factors, thereby leading to prominent therapeutic efficacy against dextran sulfate sodium-induced colitis. Benefiting from the high photothermal performance, TMNSs cause significant suppression of CT-26 tumors without obvious recurrence. This work provides a distinct paradigm to design multi-metallic nanozymes for colon disease treatment by elaborate introduction of transition metal atoms and engineering of atomic vacancies.