A Slimming/Excavating Strategy for Enhanced Intratumoral Penetration of Acid-Disassemblable NO-Releasing Nanomedicines.

Poor tumor penetration is the major predicament of nanomedicines that limits their anticancer efficacy. The dense extracellular matrix (ECM) in the tumor is one of the major barriers against the deep penetration of nanomedicines. In this work, a slimming/excavating strategy is proposed for enhanced intratumoral penetration based on an acid-disassemblable nanomicelles-assembled nanomedicine and the NO-mediated degradation of ECM.

Inhibition of free heme-catalyzed Fenton-like reaction prevents non-alcoholic fatty liver disease by hepatocyte-targeted hydrogen delivery.

The metabolic disorder of hepatocytes in non-alcoholic fatty liver disease (NAFLD) leads to the formation of an iron pool which induces the Fenton reaction-derived ferroptosis and the deterioration of liver disease. The elimination of the iron pool for the removal of Fenton reactions is vitally important to prevent the evolution of NAFLD, but quite challenging. In this work, we discover that free heme in the iron pool of NAFLD can catalyze the hydrogenation of HO/‧OH to block the heme-based Fenton reaction for the first time, and therefore develop a novel hepatocyte-targeted hydrogen delivery system (MSN-Glu) by modifying magnesium silicide nanosheets (MSN) with N-(3-triethoxysilylpropyl) gluconamide to block the heme-catalyzed vicious circle of liver disease.

Sonocatalytic hydrogen/hole-combined therapy for anti-biofilm and infected diabetic wound healing.

It is a great challenge to effectively eradicate biofilm and cure biofilm-infected diseases because dense extracellular polymeric substance matrix prevents routine antibacterial agents from penetrating into biofilm. H is an emerging energy-regulating molecule possessing both high biosafety and high tissue permeability. In this work, we propose a concept of sonocatalytic hydrogen/hole-combined 'inside/outside-cooperation' anti-biofilm for promoting bacteria-infected diabetic wound healing based on two-dimensional piezoelectric nanomaterials.

Mesocrystalline ZnS nanoparticles-augmented sonocatalytic full water splitting into H/O for immunoactivating deep tumor.

Therapeutic gas molecules have high tissue penetrability, but their sustainable supply and controlled release in deep tumor is a huge challenge. In this work, a concept of sonocatalytic full water splitting for hydrogen/oxygen immunotherapy of deep tumor is proposed, and a new kind of ZnS nanoparticles with a mesocrystalline structure (mZnS) is developed to achieve highly efficient sonocatalytic full water splitting for sustainable supply of H and O in tumor, achieving a high efficacy of deep tumor therapy. Mechanistically, locally generated hydrogen and oxygen molecules exhibit a tumoricidal effect as well as the co-immunoactivation of deep tumors through inducing the M2-to-M1 repolarization of intratumoral macrophages and the tumor hypoxia relief-mediated activation of CD8 T cells, respectively.

Injectable spontaneous hydrogen-releasing hydrogel for long-lasting alleviation of osteoarthritis.

Excessive production of reactive oxygen species (ROS) amplifies pro-inflammatory pathways and exacerbates immune responses, and is a key factor in the progression of osteoarthritis (OA). Therapeutic hydrogen gas (H) with antioxidative and anti-inflammatory effects, has a potential for OA alleviation, but the targeted delivery and sustained release of H are still challenging. Herein, we develop an injectable calcium boride nanosheets (CBN) loaded hydrogel platform (CBN@GelDA hydrogel) as a high-payload and sustainable H precursor for OA treatment.

NIR-photocatalytic regulation of arthritic synovial microenvironment.

Synovial microenvironment (SME) plays a vital role in the formation of synovial pannus and the induction of cartilage destruction in arthritis. In this work, a concept of the photocatalytic regulation of SME is proposed for arthritis treatment, and monodispersive hydrogen-doped titanium dioxide nanorods with a rutile single-crystal structure are developed by a full-solution method to achieve near infrared-photocatalytic generation of hydrogen molecules and simultaneous depletion of overexpressed lactic acid (LA) for realizing SME regulation in a collagen-induced mouse model of rheumatoid arthritis. Mechanistically, locally generated hydrogen molecules scavenge overexpressed reactive oxygen species to mediate the anti-inflammatory polarization of macrophages, while the simultaneous photocatalytic depletion of overexpressed LA inhibits the inflammatory/invasive phenotypes of synoviocytes and macrophages and ameliorates the abnormal proliferation of synoviocytes, thereby remarkably preventing the synovial pannus formation and cartilage destruction.

Homogeneous Carbon/Potassium-Incorporation Strategy for Synthesizing Red Polymeric Carbon Nitride Capable of Near-Infrared Photocatalytic H Production.

The efficient utilization of near-infrared (NIR) light for photocatalytic hydrogen generation is vitally important to both solar hydrogen energy and hydrogen medicine, but remains a challenge at present, owing to the strict requirement of the semiconductor for high NIR responsiveness, narrow bandgap, and suitable redox potentials. Here, an NIR-active carbon/potassium-doped red polymeric carbon nitride (RPCN) is achieved for by using a similar-structure dopant as the melamine (C H N ) precursor with the solid KCl. The homogeneous and high incorporation of carbon and potassium remarkably narrows the bandgap of carbon nitride (1.