Peptide-functionalized membrane camouflage for endogenous H2S-induced photothermal immunotherapy of orthotopic colorectal cancer

Abstract The significant challenges pose by the high recurrence and metastasis rates of colorectal cancer (CRC) persist in its diagnosis and treatment. Activating innate immunity in CRC treatment has the potential to reduce drug resistance and side effects. Here, we develop a biomimetic platform by utilizing antimicrobial peptide-functionalized CRC cell membranes to encapsulate a cobalt-based metal-organic framework (C), hereby called peptide-functionalized camouflage C (PfCC). When injected into tumour-bearing mice, PfCC will degrade under the acidic condition of the tumour microenvironment and release cobalt ions, which react with endogenous H 2 S to generate black stellate precipitates with good photothermal properties, recruiting NK cells and mitigates the immunosuppressive tumour-microenvironment. Simultaneously, the degradation of PfCC will release structure-protected antimicrobial peptides, inhibiting harmful bacteria, such as Desulfovibrio , and reducing H 2 S production. The abovementioned synergistic top-down regulation of H 2 S promote the polarization of macrophages and further activates the innate immune response. Moreover, experiments including the convex hull algorithm from AI deep learning of the segment anything model indicate that PfCC exhibites the most effective therapeutic effect compared with the single H 2 S-regulated therapeutic modality. Taken together, PfCC represents a potential anti-cancer therapy for CRC with the combined effect of immune-regulation and the regulation of the gut flora.