biostudies-literatureCao QMedical Research Project of China Medical and Health Development FoundationCeyuan Puhui (Ningbo) Biotechnology Co., Ltd.e00225https://www.ebi.ac.uk/biostudies/studies/S-EPMC12376508biostudies-literatureUnknown12(30)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.Advanced science (Weinheim, Baden-Wurttemberg, Germany)Nanoparticle-Mediated CXCL12-CXCR4 Inhibition Reprograms Macrophages and Suppresses Gastric Carcinoma.PMC123765086010223002JJ-2024-0546Fu RLi XGong RXiao YLv RSun DLiu QCheng XWang JCao QfalseNanoparticle-Mediated CXCL12-CXCR4 Inhibition Reprograms Macrophages and Suppresses Gastric Carcinoma.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.2025-01-01T00:00:00Z2025 Aug2026-05-09T19:15:12.427Z2026-04-08T01:11:05.308ZS-EPMC123765084053677410.1002/advs.202500225