Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response.

Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer therapy. An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via the Jahn-Teller effect induced by the introduction of Cu2+, and the synthesized ZCA NSs regulated the intricate tumor microenvironment (TME) by depleting endogenous glutathione (GSH) to amplify oxidative stress for further enhanced SDT performance. Furthermore, cuproptosis was evoked by intracellular overload of Cu2+ and amplified by SDT, leading to irreversible proteotoxicity. In vitro results showed that such synergetic SDT/cuproptosis triggered immunogenic cell death (ICD) and promoted the maturation of dendritic cells (DCs). Furthermore, the as-synthesized ZCA NS-mediated SDT/cuproptosis thoroughly eradicated the in vivo solid tumors and simultaneously elicited antitumor immunity to suppress lung and liver metastasis. Overall, this work established a nanoplatform for synergistic SDT/cuproptosis with a satisfactory antitumor immunity.

Orally Administered Silicon Hydrogen Nanomaterials as Target Therapy to Treat Intestinal Diseases.

The occurrence and development of inflammatory bowel diseases (IBDs) are inextricably linked to the excessive production of reactive oxygen species (ROS). Thus, there is an urgent need to develop innovative tactics to combat IBDs and scavenge excess ROS from affected areas. Herein, silicon hydrogen nanoparticles (SiH NPs) with ROS-scavenging ability were prepared by etching Si nanowires (NWs) with hydrogen fluoride (HF) to alleviate the symptoms associated with IBD by orally targeting the inflamed colonic sites. The strong reductive Si-H bonds showed excellent stability in the gastric and intestinal fluids, which exhibited efficient ROS-scavenging effects to protect cells from high oxidative stress-induced death. After oral delivery, the negatively charged SiH NPs were specifically adsorbed to the positively charged inflammatory epithelial tissues of the colon for an extended period via electrostatic interactions to prolong the colonic residence time. SiH NPs exhibited significant preventive and therapeutic effects in dextran sodium sulfate-induced prophylactic and therapeutic mouse models by inhibiting colonic shortening, reducing the secretion of pro-inflammatory cytokines, regulating macrophage polarization, and protecting the colonic barrier. As determined using 16S rDNA high-throughput sequencing, the oral administration of SiH NPs treatment led to changes in the abundance of the intestinal microbiome, which improved the bacterial diversity and restored the relative abundance of beneficial bacteria after the inflamed colon. Overall, our findings highlight the broad application of SiH-based anti-inflammatory drugs in the treatment of IBD and other inflammatory diseases.

Bioactive Vanadium Disulfide Nanostructure with "Dual" Antitumor Effects of Vanadate and Gas for Immune-Checkpoint Blockade-Enhanced Cancer Immunotherapy.

Bioactive inorganic nanomaterials and the biological effects of metal ions have attracted extensive attention in tumor therapy in recent years. Vanadium (V), as a typical bioactive metal element, regulates a variety of biological functions. However, its role in antitumor therapy remains to be revealed. Herein, biodegradable vanadium disulfide (VS2) nanosheets (NSs) were prepared as a responsive gas donor and bioactive V source for activating cancer immunotherapy in combination with immune-checkpoint blockade therapy. After PEGylation, VS2-PEG exhibited efficient glutathione (GSH) depletion and GSH-activated hydrogen sulfide (H2S) release. Exogenous H2S caused lysosome escape and reduced adenosine triphosphate (ATP) synthesis in tumor cells by interfering with the mitochondrial membrane potential and inducing acidosis. In addition, VS2-PEG degraded into high-valent vanadate, leading to Na+/K+ ATPase inhibition, potassium efflux, and interleukin (IL)-1ß production. Together with further induction of ferroptosis and immunogenic cell death, a strong antitumor immune response was stimulated by reversing the immunosuppressive tumor microenvironment. Moreover, the combined treatment of VS2-PEG and α-PD-1 amplified antitumor therapy, significantly suppressed tumor growth, and further elicited robust immunity to effectively defeat tumors. This work highlights the biological effects of vanadium for application in cancer treatment.

Calcium Hydride-Based Dressing to Promote Wound Healing.

Wound microenvironment with excess reactive oxygen species (ROS) can significantly inhibit wound healing. Encouraged by hydrogen molecules (H2 ) with effective ROS scavenging and calcium hydride (CaH2 ) with sufficient H2 supply, the authors for the first time employed CaH2 as a therapeutic H2 donor and starch as a diluent to construct CaH2 pulvis dressing for wound healing treatment. It has been found that CaH2 by generating H2 exhibited excellent ROS scavenging performance, favorable for preserving the oxidative-stress-induced cell death. After being applied onto the skin wound, the CaH2 pulvis dressing with the unique ROS-scavenging ability can accelerate skin wound healing in healthy/diabetic mice (small animal models) and Bama mini-pigs (large animal model). Such CaH2 dressing can release H2 to relieve the inflammation levels, decrease the secretion of pro-inflammatory cytokines, increase the infiltration of inflammation-suppressive immune cells, and promote the regeneration of new blood vessels and collagens, thereby accelerating wound healing. This work highlighted that the integration of anti-oxidation and anti-inflammation functions based on CaH2 dressing endowed it with a promising possibility for the treatment of inflammatory diseases.

Inferring the role of pit membranes in solute transport from solute exclusion studies in living conifer stems.

The functional role of pits between living and dead cells has been inferred from anatomical studies but amassing physiological evidence has been challenging. Centrifugation methods were used to strip water from xylem conduits, permitting a more quantitative gravimetric determination of the water and solid contents of cell walls than is possible by more traditional methods. Quantitative anatomical evidence was used to evaluate the water volume in xylem conduits and the water content of living cells. Quantitative perfusion of stems with polyethylene glycol of different molecular weight was used to determine the solute-free space. We measured the portioning of water and solute-free space among anatomical components in stems and demonstrated that lignin impeded the free movement of solutes with molecular weight >300. Hence, movement of large solutes from living cells to xylem conduits is necessarily confined to pit structures that permit transmembrane solute transport via primary walls without lignin. The functional role of pits was additionally indicated by combining data in this paper with previous studies of unusual osmotic relationships in woody species that lack pits between dead wood fibers and vessels. The absence of pits, combined with the evidence of exclusion of solutes of molecular weight >300, explains the unexpected osmotic properties.