Evaluation of the anti-tumor effect of gambogic acid loaded macrophage membranes nanoparticles combined with radiotherapy and anti-PD-1mAb in the colorectal cancer with liver metastasis model

作者：Xin Zhang, Li Li, Haiqing Niu, Zixin Liang, Liuqi Sang, Ning Wang, Fengli Huang, Xingzhi Han, Zhihao Liu, Xiao Shi, Qun Zhang, Jing Hu, Xiaoping Qian · 发表于：Biomaterials Advances · 年份：2025 · DOI：10.1016/j.bioadv.2025.214463 · 被引用次数：4 · 研究领域：Natural Compound Pharmacology Studies、Magnolia and Illicium research、Autophagy in Disease and Therapy

BACKGROUND: The prognosis of patients with colorectal liver metastasis (CRLM) is poor. The 5-year survival rate of those who cannot be treated by surgery is less than 5 %, thus, the management of patients with CRLM remains a significant challenge. Based on the anti-tumor activity of traditional Chinese medicine monomer and the local immune activation caused by low dose radiotherapy combined with immune checkpoint inhibitors, we jointly applied it to explore the tumor inhibitory effect and the change of local immune microenvironment in liver metastasis model. METHODS: We engineered biomimetic nanoparticles through macrophage membrane encapsulation of gambogic acid (GA)-loaded PLGA cores, employing a double emulsion-solvent evaporation method to fabricate M-PLGA@GA nanoparticles. In tumor-bearing mice with surgically induced colorectal liver metastasis via hemisplenectomy, therapeutic efficacy was evaluated through intratumoral administration of M-PLGA@GA combined with triple-modality therapy: low-dose radiotherapy (LDRT; 5 Gy), anti-programmed cell death protein 1 monoclonal antibody (anti-PD-1 mAb; 200 μg), and nanoparticle delivery. This combinatorial approach leveraged spatial-temporal control of tumor microenvironment modulation. RESULTS: The nanoparticles augmented the targeted delivery ability of drugs to tumor cells and in vivo circulation duration, coupled with improved aqueous solubility of the encapsulated therapeutic agent, all while preserving its therapeutic poten...