Cao Qianqian, Cheng Xiaolei, Lv Rongbin, Sun Dianshui, Wang Jihua, Fu Runjia, Gong Rumei, Xiao Yueying, Liu Qin, Li Xiaomei
Cancer Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, P. R. China.
Department of Oncology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, 266042, P. R. China.
Adv Sci (Weinh). 2025 Aug;12(30):e00225. doi: 10.1002/advs.202500225. Epub 2025 Jun 19.
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.
胃癌（GC）仍然是一项重大的全球健康挑战，需要新的治疗方法。本研究调查了自组装的M2pep-Cs纳米粒子/普乐沙福纳米颗粒通过靶向CXCL12-CXCR4信号通路并重新编程肿瘤相关巨噬细胞（TAM）以增强抗肿瘤免疫力来抑制胃癌的疗效。使用透射电子显微镜、动态光散射和生物学检测评估纳米颗粒的物理化学性质和生物相容性。建立胃癌小鼠模型，随后进行组织学和免疫组织化学分析以评估肿瘤凋亡和增殖。包括转录组学、蛋白质组学和代谢组学在内的多组学方法可识别受治疗影响的关键基因和信号通路。流式细胞术和酶联免疫吸附测定法可定量免疫激活标志物；同时，细胞迁移和侵袭试验评估肿瘤抑制效果。结果表明，M2pep-Cs纳米粒子/普乐沙福可有效调节肿瘤微环境，通过抑制CXCL12-CXCR4对TAM进行重新编程，增强免疫识别和T细胞反应，从而抑制胃癌进展。本研究提供了机制方面的见解，并突出了基于纳米颗粒的免疫疗法对胃癌的潜力，为临床转化提供了一条有前景的途径。
