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. A nanozyme-loaded microneedle-patch is designed for "trans-surgical bed" catalytic therapy and construction of autologous cancer vaccine. Aided by microneedle-delivery, the nanozyme can sustainably respond to H2O2 and GSH and produce reactive oxygen species. The in situ catalysis has constructed the effective in situ tumor vaccine by inducing immunogenic cell death, macrophage repolarization, and finally long-term immune-memory against tumor-rechallenging. image