Tumor microenvironment-responsive arsenic-loaded layered double hydroxides film with synergistic anticancer and bactericidal activity

Malignant obstruction makes gallbladder cancer have a high mortality rate. Nickel–titanium alloy (nitinol) stents are commonly used as a local intervention to maximize patient survival time, but the stents lack antitumor and antibacterial capacity and are vulnerable to secondary obstruction. Arsenic-based drugs show good therapeutic promise against gallbladder cancer. To meet clinical needs, the layered double hydroxides (LDHs) film is constructed on the nitinol, whose arsenite loading amounts rose by 60% after simple heat treatment compared with the conventional anion-exchange strategy. In addition, calcination promotes the dissolution of nickel ions from the LDHs lattice, resulting in a powerful synergistic killing effect on tumor cells together with the released arsenic. More importantly, the calcined arsenic-loaded LDHs are sensitive to the acidic microenvironment of tumor tissues, which presents a much lower arsenic and nickel release amount in the normal tissues, guaranteeing its biosafety. Meanwhile, the vertically sharp LDHs nanosheets can synergize with arsenic to achieve effective physical cleavage and chemical killing of adherent and planktonic bacteria. In short, we attempt to use arsenic drugs for local interventions and reasonably avoid their toxic side effects, which provides a new design idea for nitinol stents applied in the treatment of gallbladder cancer.