Ultrasound-Driven Piezoelectrocatalytic Immunoactivation of Deep Tumor. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Tumor heterogeneity makes routine drugs difficult to penetrate solid tumors, limiting their therapy efficacies. Based on high tissue penetrability of hydrogen molecules (H ) and ultrasound (US) and the immunomodulation effects of H and lactic acid (LA), this work proposes a novel strategy of US-driven piezoelectrocatalytic tumor immunoactivation for high-efficacy therapy of deep tumors by piezoelectrocatalytic hydrogen generation and LA deprivation. A kind of US-responsive piezoelectric SnS nanosheets (SSN) is developed to realize US-triggered local hydrogen production and simultaneous LA deprivation in deep tumors. The proof-of-concept experiments which are executed on an orthotopic liver cancer model have verified that intratumoral SSN-medicated piezoelectrocatalytically generated H liberates effector CD8 T cells from the immunosuppression of tumor cells through down-regulating PD-L1 over-expression, and simultaneous LA deprivation activates CD8 T cells by inhibiting regulatory T cells, efficiently co-activating tumor immunity and achieving a high outcome of liver tumor therapy with complete tumor eradication and 100% mice survival. The proposed strategy of US-driven piezoelectrocatalytic tumor immunoactivation opens a safe and efficient pathway for deep tumor therapy. 10.1002/advs.202303016

Nanocapsule-mediated sustained H release in the gut ameliorates metabolic dysfunction-associated fatty liver disease. Jin Zhaokui,Sun Yuan,Yang Tian,Tan Lunbo,Lv Peixun,Xu Qingqing,Tao Geru,Qin Shucun,Lu Xifeng,He Qianjun Biomaterials Metabolic dysfunction-associated fatty liver disease (MAFLD) is estimated to affect a quarter of all population and represents a major health threat to all societies. Yet, currently no approved pharmacological treatment is available for MAFLD. H-rich water has recently been reported to reduce hepatic lipid accumulation in MAFLD patients but its efficacy is limited due to low H dosage. Increasing H dose may enhance its therapeutic effects but remains technically challenging. In this study, we designed and synthesized a hydrogen nanocapsule by encapsulating ammonia borane into hollow mesoporous silica nanoparticles to achieve ultrahigh and sustained H release in the gut. We then investigated its efficacy in treating early-stage MAFLD and other metabolic dysfunctions such as obesity and diabetes. The hydrogen nanocapsule attenuated both diet-induced and genetic mutation induced early-stage MAFLD, obesity, and diabetes in mice, without any tissue toxicity. Mechanistically, we discovered that sustained and ultrahigh H supply by hydrogen nanocapsule increased, among other species, the abundance of Akkermansia muciniphila, highlighting reshaped gut microbiota as a potential mechanism of H in treating metabolic dysfunctions. Moreover, hepatic transcriptome showed a reprogramed liver metabolism profile with reduced lipid synthesis and increased fatty acid metabolism. 10.1016/j.biomaterials.2021.121030

Local H release remodels senescence microenvironment for improved repair of injured bone. Nature communications The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H-releasing scaffold which can release high-dosage H (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi nanoparticles onto mesoporous bioactive glass. We demonstrate efficient remodeling of the microenvironment and enhanced repair of critical-size bone defects in an aged mouse model. Mechanistically, we reveal that local H release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H alleviates the progression of aging/injury-superposed senescence, facilitates the recruitment of endogenous cells and the preservation of their regeneration capability, thereby creating a pro-regenerative microenvironment able to support bone defect regeneration. 10.1038/s41467-023-43618-z

An Activity-Based Ratiometric Fluorescent Probe for In Vivo Real-Time Imaging of Hydrogen Molecules. Gong Wanjun,Jiang Lingdong,Zhu Yanxia,Jiang Mengna,Chen Danyang,Jin Zhaokui,Qin Shucun,Yu Zhiqiang,He Qianjun Angewandte Chemie (International ed. in English) To reveal the biomedical effects and mechanisms of hydrogen molecules urgently needs hydrogen molecular imaging probes as an imperative tool, but the development of these probes is extremely challenging. A catalytic hydrogenation strategy is proposed to design and synthesize a ratiometric fluorescent probe by encapsulating Pd nanoparticles and conjugating azido-/coumarin-modified fluorophore into mesoporous silica nanoparticles, realizing in vitro and in vivo fluorescence imaging of hydrogen molecules. The developed hydrogen probe exhibits high sensitivity, rapid responsivity, high selectivity and low detection limit, enabling rapid and real-time detection of hydrogen molecules both in cells and in the body of animal and plant. By application of the developed fluorescent probe, we have directly observed the super-high transmembrane and ultrafast transport abilities of hydrogen molecules in cells, animals and plants, and discovered in vivo high diffusion of hydrogen molecules. 10.1002/anie.202114594