Porphyrin-Decorated Cu₂O-Encapsulated Metal–Organic Frameworks as pH-Sensitive Biomimetic Catalysts for Mediating Nitric Oxide Production

Nitric oxide (NO) is an important radical gaseous signal molecule generated by nitric oxide synthase (NOS) enzymes that participates under various physiological and biological functions and has many roles in signal transduction and cancer therapy. Interestingly, the NO levels which could be maintained by l-arginine (l-arg) and S-nitrosothiols (RSNO) play a vital role in the maintenance of normal physiology functions. However, the controlled production of NO under physiological pH remains a challenge. Herein, we report pH-responsive multifunctional nanoplatforms based on porphyrin (FePor)-decorated cuprous oxide (Cu2O)-encapsulated metal–organic frameworks (ZIF-8) and then modify with poly-l-arginine (P-Arg) for mediating the synthesis of NO. Under acid conditions in tumor, Cu2O/FePor@ZIF-8@Arg is broken down to rapidly release the composite of Cu2O/FePor and P-Arg. Cu2O in the unprotected Cu2O/FePor reacts with RSNO to generate both NO and Cu2+. FePor in Cu2O/FePor could act as artificial enzymes for catalyzing the oxidation of P-Arg to produce NO under physiological pH. The results implied that the efficient production of NO could induce cancer cell apoptosis. The presented strategy supplies a promising method for designing and constructing multifunctional nanoplatforms for the development of NO therapeutic strategy.