靶向M2巨噬细胞的纳米药物体内抗肿瘤效应的初步研究  

Preliminary study on the anti-tumor effect of nanoparticles targeting M2 macrophages in vivo

作　　者：李逸娴 黄燕 蒋鸥 LI Yi-xian;HUANG Yan;JIANG Ou(Department of Oncology,the Affiliated Hospital of Southwest Medical University,Luzhou 646000;Cancer Center,the Second People's Hospital of Neijiang,Neijiang 641000,Sichuan,China)

机构地区：[1]西南医科大学附属医院肿瘤科,四川泸州646000 [2]内江市第二人民医院肿瘤中心,四川内江641000

出　　处：《川北医学院学报》2023年第4期444-450,共7页Journal of North Sichuan Medical College

基　　金：国家科技重大专项-重大新药创制项目(2018ZX09303-014)。

摘　　要：目的:探索靶向M2巨噬细胞的纳米复合物(MICE-NPs)在BALB/c小鼠肿瘤模型中的抑瘤效应及其相关机制。方法:建立BALB/c小鼠肿瘤模型,通过免疫组化法观察癌巢周围肿瘤相关巨噬细胞(TAMs)的聚集情况;采用不同浓度纳米药物在小鼠体内进行急性毒性实验,从而获得后续实验纳米药物的合适浓度;利用荧光显微镜观察纳米药物在小鼠不同组织中的分布情况;通过肿瘤控制率的计算,评估MICE-NPs对小鼠肿瘤生长的抑制作用;采用流式细胞技术观察MICE-NPs对荷瘤小鼠病灶内免疫细胞组成的影响。结果:免疫组化结果表明,模型小鼠肿瘤微环境(TME)中存在大量TAMS及M2型巨噬细胞。急性毒性实验表明,MICE-NPs急性期毒性不明显,MICE-NPs具较好的安全性。荧光显微镜观察到在给药后24 h仍可于肿瘤组织中观察到较高水平的荧光显示,证明MICE-NPs可在肿瘤组织中蓄积。MICE-NPs的抑瘤实验证明高浓度MICE-NPs抑瘤效果良好。流式细胞仪结果显示,与对照组相比,纳米药物组小鼠的肿瘤组织中M2、Treg的比例下降,M1、CTL比例升高。结论:MICE-NPs体内实验未见明显毒副作用,抑瘤效应良好,有望能为肿瘤治疗提供一种新的思路与方法。Objective:To explore the antitumor effect of nanocomplex(MICE-NPs)targeting M2 macrophages in BALB/c mouse tumor models and explore its related mechanisms.Methods:BALB/c mouse tumor models were established to observe the accumulation of tumor-associated macrophages(TAMs)around the cancer nests by immunohistochemistry,acute toxicity experiments were performed in mice using different concentrations of nanomedicines to obtain the appropriate concentration of nanomedicines for subsequent experiments.The distribution of nanomedicines in different tissues of mice was observed using fluorescence microscopy,the inhibitory effect of MICE-NPs on tumor growth in mice was assessed by the calculation of tumor control rate,flow cytometry was used to observe the effect of MICE-NPs on the composition of immune cells in the lesions of tumor-bearing mice.Results:The immunohistochemical results showed that there were a large number of TAMS and M2 macrophages in the tumor microenvironment(TME)of the model mice.The acute toxicity test showed that MICE-NPs had no obvious acute toxicity,and MICE-NPs had good safety.Fluorescence microscopy showed that a high level of fluorescence was still observed in tumor tissue 24 hours after administration,indicating that MICE-NPs could accumulate in tumor tissue.The tumor inhibitory experiment of MICE-NPs demonstrated that high concentrations of MICE-NPs had good tumor inhibitory effect.Flow cytometry results showed that the proportion of M2 and Treg decreased,while the proportion of M1 and CTL increased in the tumor tissues of mice in the nanomedicine group compared with the control group.Conclusion:MICE-NPs showed no significant toxicity and good antitumor effect in vivo,which is expected to provide a new idea and method for tumor treatment.

关 键 词：纳米颗粒 甘露糖受体 M2型巨噬细胞 肿瘤相关巨噬细胞 体内实验 

分 类 号：R979.1[医药卫生—药品]