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

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

Abstract 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 CK...

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Main Authors: Zheng Zhao, Jingyun Wang, Mengmeng Liu, Ziqian Li, Fei Cao, Pengfei Xu, Qi Fang, Jie Yang, Zhulong Hu, Di Wu, Rongbin Liu, Xuekui Liu
Format: Article
Language:English
Published: BMC 2025-03-01
Series:BMC Cancer
Subjects:
Neuropilin1
Cell-permeable peptides
Anti-tumor
Pyroptosis
Immunotherapy
Online Access:https://doi.org/10.1186/s12885-025-13784-y
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Summary:Abstract 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.
ISSN:1471-2407

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