Turning Threat to Therapy: A Nanozyme-Patch in Surgical Bed for Convenient Tumor Vaccination by Sustained In Situ Catalysis.

Complete surgical resection of tumor is difficult as the invasiveness of cancer, making the residual tumor a lethal threat to patients. The situation is deteriorated by the immune suppression state after surgery, which further nourishes tumor recurrence and metastasis. Immunotherapy is promising to combat tumor metastasis, but is limited by severe toxicity of traditional immunostimulants and complexity of multiple functional units. Here, it is reported that the simple "trans-surgical bed" delivery of Cu2- xSe nanozyme (CSN) by a microneedle-patch can turn the threat to therapy by efficient in situ vaccination. The biocompatible CSN exhibits both peroxidase and glutathione oxidase-like activities, efficiently exhausting glutathione, boosting free radical generation, and inducing immunogenic cell death. The once-for-all inserting of the patch on surgical bed facilitates sustained catalytic action, leading to drastic decrease of recurrence rate and complete suppression of tumor-rechallenge in cured mice. In vivo mechanism interrogation reveals elevated cytotoxic T cell infiltration, re-educated macrophages, increased dendritic cell maturation, and memory T cells formation. Importantly, preliminary metabolism and safety evaluation validated that the metal accumulation is marginable, and the important biochemical indexes are in normal range during therapy. This study has provided a simple, safe, and robust tumor vaccination approach for postsurgical metastasis control.

Potent intrinsic bactericidal activity of novel copper telluride nano-grape clusters with facile preparation.

Bactericidal nanomedicines often suffer from a complicated design and insufficient intrinsic inhibitory efficacy. Herein, novel anti-bacterial copper telluride (CuTe) nano-clusters are reported, featuring superior bactericidal efficiency, facile preparation, and unique mechanism. These nanoparticles, well dispersable in water, resembled grape clusters with rough surfaces. The CuTe nano-grape clusters exhibited ultra-high sterilization efficacy at ultra-low concentration, particularly for Gram-negative bacteria, and were more potent than conventional anti-microbial nanoparticles. Also, the grape clusters effectively inhibited the bacterial biofilm development. Further investigation revealed the synergized mechanisms of reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Interestingly, electron microscopy revealed that the grape clusters served as bacterial hunters by tightly adhering to bacterial surfaces. The bacteria subsequently suffered from the leakage of various intracellular components including nucleic acid, proteins, and potassium. Most encouragingly, CuTe drastically reduced bacterial number in a mouse model with lethal intraperitoneal infection and increased the mouse survival rate to 90%. This finding could inspire the development of highly potent bactericidal inorganic formulations with simplified structure, multiple antibacterial mechanisms, and promising application potential.