Biomimetic nanozymes catalyze cascade reactions for enhanced tumor nanocatalytic therapy†

Nano-catalytic therapy is an emerging tumor therapeutic strategy that has received considerable attention in recent years. This approach can convert endogenous hydrogen peroxide (H₂O₂) at the tumor site into highly toxic hydroxyl radicals (˙OH) via a Fenton or Fenton-like reaction catalyzed by metal ions. However, the low levels of ˙OH generated merely from endogenous H₂O₂ are usually insufficient to effectively kill cancer cells. To address this limitation, we developed an efficient biomimetic nanozyme (HMPB/LAP@TK-CCM) designed to amplify intracellular oxidative stress and alleviate tumor hypoxia for enhanced nano-catalytic therapy. This nanozyme is loaded with the anticancer drug β-lapachone (LAP), which increases H₂O₂ levels within the tumor cells, thus enhancing the Fenton reaction of HMPB. The camouflaging strategy using a cancer-thylakoid hybrid membrane reduces the immune clearance of the nanoparticles and promotes their accumulation at the tumor site. The thylakoid membrane (TK) also contains natural catalase, which alleviates tumor hypoxia by producing oxygen, thus facilitating the generation of H₂O₂ by LAP and further enhancing the synergistic anti-tumor effect. Furthermore, in vivo studies demonstrated that HMPB/LAP@TK-CCM NPs effectively restrain tumor progression without negatively impacting normal tissues.