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

Sensitive Electrochemical Sensor for Glycoprotein Detection Using a Self-Serviced-Track 3D DNA Walker and Catalytic Hairpin Assembly Enzyme-Free Signal Amplification

Approaches for the detection of targets in the cellular microenvironment have been extensively developed. However, developing a method with sensitive and accurate analysis for noninvasive cancer diagnosis has remained challenging until now. Here, we reported a sensitive and universal electrochemical platform that integrates a self-serviced-track 3D DNA walker and catalytic hairpin assembly (CHA) triggering G-Quadruplex/Hemin DNAzyme assembly signal amplification. In the presence of a target, the aptamer recognition initiated the 3D DNA walker on the cell surface autonomous running and releasing DNA (C) from the triple helix. The released DNA C as the target-triggered CHA moiety, and then G-quadruplex/hemin, was formed on the surface of electrode. Eventually, a large amount of G-quadruplex/hemin was formed on the sensor surface to generate an amplified electrochemical signal. Using N-acetylgalactosamine as a model, benefiting from the high selectivity and sensitivity of the self-serviced-track 3D DNA walker and the CHA, this designed method showed a detection limit of 39 cell/mL and 2.16 nM N-acetylgalactosamine. Furthermore, this detection strategy was enzyme free and exhibited highly sensitive, accurate, and universal detection of a variety of targets by using the corresponding DNA aptamer in clinical sample analysis, showing potential for early and prognostic diagnostic application

pH-Responsive Multifunctional Nanoplatforms with Reactive Oxygen Species-Controlled Release of CO for Enhanced Oncotherapy

Recently, various nanomaterials have drawn increasing attention for enhanced tumor therapy. However, a lack of tumor uptake and insufficient generation of cytotoxic agents have largely limited the antitumor efficacy in vivo. Herein, a multifunctional nanoplatform (IL@CPPor­(CO)) was constructed with pH-responsive copper peroxide nanoparticles (CPNP) that are capable of self-supplying H2O2, a radical-sensitive carbonic oxide (CO) donor (Fe3(CO)12), photosensitizer Iridium­(III) meso-tetra (N-methyl-4-pyridyl)­porphyrin pentachloride (IrPor), and ionic liquid (IL) for enhanced oncotherapy. Under acidic conditions, the CPNP could decompose to release H2O2 and Cu2+. The concomitant generation of H2O2 could efficiently trigger Fe3(CO)12 to release the CO in situ. On the other hand, Cu2+ possesses both glutathione depletion and Fenton-like properties. In addition, IrPor has both peroxidase-like activity and photosensitizer properties to produce reactive oxygen species (ROS) in tumors. The released ROS could trigger the rapid intracellular release of CO. More importantly, released CO and ROS could promote cell apoptosis and improve the therapeutic efficacy. Moreover, due to the pH-dependent ROS generation property, the IL@CPPor­(CO) exhibited high tumor accumulation, low toxicity, and good biocompatibility, which enabled effective tumor growth inhibition with minimal side effects in vivo. This work provides a novel multifunctional nanoplatform that combined photodynamic therapy with CDT and CO to improve therapeutic efficacy