2. Academic Validation
  3. Nanoparticle-Mediated CXCL12-CXCR4 Inhibition Reprograms Macrophages and Suppresses Gastric Carcinoma

Nanoparticle-Mediated CXCL12-CXCR4 Inhibition Reprograms Macrophages and Suppresses Gastric Carcinoma

  • Adv Sci (Weinh). 2025 Jun 19:e00225. doi: 10.1002/advs.202500225.
Qianqian Cao 1,  Xiaolei Cheng 2,  Rongbin Lv 3,  Dianshui Sun 1,  Jihua Wang 1,  Runjia Fu 1,  Rumei Gong 1,  Yueying Xiao 4,  Qin Liu 1,  Xiaomei Li 5
Affiliations

Affiliations

  • 1 Cancer Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, P. R. China.
  • 2 Department of Oncology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, 266042, P. R. China.
  • 3 Postdoctoral workstation, Liaocheng People's Hospital, No. 67, Dongchang West Road, Liaocheng, 252000, P. R. China.
  • 4 Department of Spine Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, P. R. China.
  • 5 Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, P. R. China.
PMID: 40536774 DOI: 10.1002/advs.202500225
Abstract

Gastric carcinoma (GC) remains a major global health challenge, requiring novel therapeutic approaches. This study investigates the efficacy of self-assembled M2pep-Cs NPs/Plerixafor nanoparticles in suppressing GC by targeting the CXCL12-CXCR4 signaling pathway and reprogramming tumor-associated macrophages (TAMs) to enhance anti-tumor immunity. The nanoparticles' physicochemical properties and biocompatibility are assessed using transmission electron microscopy, dynamic light scattering, and biological assays. A GC mouse model is established, followed by histological and immunohistochemical analyses to evaluate tumor Apoptosis and proliferation. Multi-omics approaches, including transcriptomics, proteomics, and metabolomics, identify key genes and pathways affected by treatment. Flow cytometry and ELISA quantify immune activation markers; while, cell migration and invasion assays evaluate tumor suppression effects. The results demonstrate that M2pep-Cs NPs/Plerixafor effectively modulates the tumor microenvironment, suppressing GC progression by reprogramming TAMs through CXCL12-CXCR4 inhibition, enhancing immune recognition and T cell responses. This study provides mechanistic insights and highlights the potential of nanoparticle-based immunotherapy for GC, offering a promising avenue for clinical translation.

Keywords

CXCL12–CXCR4 signaling pathway; M2pep‐Cs NPs/plerixafor nanoparticles; gastric carcinoma; immunotherapy; macrophage reprogramming.

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