2. Academic Validation
  3. Targeting S100A8/A9-NCF1 axis in tumor microenvironment to prevent tumor metastasis by self-assembled peptide nanofibers

Targeting S100A8/A9-NCF1 axis in tumor microenvironment to prevent tumor metastasis by self-assembled peptide nanofibers

  • Mol Ther. 2025 Mar 3:S1525-0016(25)00167-4. doi: 10.1016/j.ymthe.2025.02.042.
Yajing Guo 1,  Zhifei Zhang 1,  Hongxia Huang 1,  Ye Wu 1,  Lixin Yin 1,  Yang Zhou 1,  Feiqing Ding 1,  Sheng Hong 1,  Nicole F Steinmetz 2,  Hui Cai 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, 66 Gongchanglu Road, Guangming District, Shenzhen 518107, China.
  • 2 Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Center for Nano Immuno-Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory University of California, San Diego, La Jolla, CA 92093, USA.
  • 3 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, 66 Gongchanglu Road, Guangming District, Shenzhen 518107, China. Electronic address: caihui5@mail.sysu.edu.cn.
PMID: 40040282 DOI: 10.1016/j.ymthe.2025.02.042
Abstract

The immunosuppressive microenvironment plays a crucial role in driving and accelerating tumor metastasis. S100A8/A9, produced by myeloid-derived suppressor cells, is a potential therapeutic target for metastatic Cancer due to its role in promoting premetastatic niche formation. Previous studies have revealed that the S100A9-targeted peptide (H6, MEWSLEKGYTIK) fused to the Fc region of mouse IgG2b Antibodies exhibits antitumor effects; however, the mechanism remains unclear. Here, dual-function peptide nanofibers (H6-Q11) were constructed, consisting of peptide H6 and self-assembly peptide (Q11, QQKFQFQFEQQ), which achieved high avidity for S100A9. In vivo studies showed that H6-Q11 nanofibers significantly prolonged lung retention and inhibited pulmonary metastasis from melanoma and breast Cancer without obvious toxicity. Immunological analyses indicated that treatment with H6-Q11 nanofibers decreased the infiltration of immunosuppressive cells while promoting the recruitment of immune effector cells to the lungs, potentially correlated with disturbances of S100A8/A9-NCF1 signaling in the tumor microenvironment. Our findings support a potential clinical application of S100A9-targeted peptide nanofibers as candidate nanomedicine for inhibiting tumor metastasis.

Keywords

S100A9; immunotherapy; self-assembly; tumor metastasis; tumor microenvironment.

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