Functionalized Amyloid-like Protein Nanofilm Mediated Synergistic Disulfidptosis and PDT for Preventing Postoperative Recurrence of Colorectal Cancer

CRC has a postoperative recurrence rate of up to 50%. Local treatment at the surgical site offers a new strategy to prevent recurrence, minimizing systemic side effects. However, these treatments often face issues like poor stability, insufficient targeting, and significant local side effects. Research shows glucose starvation can induce disulfidptosis, a novel cell death pathway, in CRC cells, suitable for precise intervention in residual tumor cells post-surgery. Our study develops a biocompatible 2D therapeutic platform using amyloid-like protein nanofilm technology for precise local synergistic intervention in disulfidptosis and PDT after CRC surgery. The nanofilm boasts excellent drug-loading capacity, enzyme activity retention, ultra-thin dimensions, wet adhesion, and biocompatibility. A model simulating incomplete tumor resection post-CRC surgery shows that the GCI@nanofilm effectively inhibits recurrence through an enzyme-catalyzed cascade reaction inducing disulfidptosis and synergizing with PDT. GCI@nanofilm overcomes challenges in local intervention, providing a foundation for precise and efficient treatment of residual tumors.