Neuropilin-1-target self-assembled peptide nanoparticles contribute to tumor treatment by inducing pyroptosis.

BACKGROUND: Expression of the Neuropilin-1 (NRP1) is reported in malignant cells of multiple human tumor types represented as a tumor marker. Targeting NRP1 with a peptide, CK3, is used for tumor molecular imaging, raising the question of the therapeutic potential of CK2, a peptide with a CK3 backbone which enhanced targeting and tumor enrichment properties. METHODS: The tumor targeting and enrichment capacity of CK2 was detected by IncuCyte, flow cytometry and animal living imaging. To enhance its therapeutic efficacy, we developed a self-assembling peptide nanoparticles Fmoc-Gffy-AP-CK2, incorporating a peptide protective domain (Fmoc), a self-assemble domain (Gffy) and an anti-tumor peptide (AP). In vitro cellular assays and in vivo tumor-xenograft experiments were conducted to evaluate the anti-tumor effect of Fmoc-Gffy-AP-CK2. RESULTS: While CK3 peptide specifically targets NRP1 in vitro and in vivo, CK2 markedly achieves stronger binding with NRP1 and higher tumor accumulation. Fmoc-Gffy-AP-CK2 exhibits a potent NRP1-dependent cytotoxic effect in vitro and in vivo. Mechanically, Fmoc-Gffy-AP-CK2 triggered caspase3/gasdermin E (GSDME)-mediated pyroptosis. Fmoc-Gffy-AP-CK2 also promotes the response rate of PD-1 checkpoint blockade. CONCLUSIONS: CK2, When combined with Fmoc-Gffy-AP domain, Demonstrated high anti-tumor efficacy, Providing a novel strategy for tumor treatment.