Ag_(2)Se纳米颗粒通过清除牙龈卟啉单胞菌抑制食管癌恶性进展  

Ag_(2)Se nanoparticles suppress growth of murine esophageal cancer allograft in mice by eliminating Porphyromonas gingivalis

作　　者：赵亚莉 李佳怡 谷变利 陈攀[1] 张理 张小漫 杨平娟 石林林 高社干[1] ZHAO Yali;LI Jiayi;GU Bianli;CHEN Pan;ZHANG Li;ZHANG Xiaoman;YANG Pingjuan;SHI Linlin;GAO Shegan(Clinical Medicine College,First Affiliated Hospital,Henan Provincial Key Laboratory of Microecology and Esophageal Cancer Prevention and Treatment,Henan Provincial Key Laboratory of Tumor Epigenetics,Henan University of Science and Technology,Luoyang 471003,China;School of Basic Medical and Forensic Sciences,Henan University of Science and Technology,Luoyang 471023,China)

机构地区：[1]河南科技大学临床医学院//河南科技大学第一附属医院//河南省微生态与食管癌防治重点实验室//河南省肿瘤表观遗传重点实验室,河南洛阳471003 [2]河南科技大学基础医学与法医学院,河南洛阳471023

出　　处：《南方医科大学学报》2025年第2期245-253,共9页Journal of Southern Medical University

基　　金：国家自然科学基金(82302966);河南省医学科技攻关省部共建重点项目(SBGJ202102199,LHGJ20230455);河南省省级科技研发计划联合基金(232103810048);洛阳市社会发展公益专项(2302016A,2302016Y)。

摘　　要：目的探讨Ag_(2)Se纳米颗粒清除食管癌胞内牙龈卟啉单胞菌(P.gingivalis)的有效性,并研究清除P.gingivalis后对食管癌恶性进展的影响。方法采用化学合成法制备Ag_(2)Se纳米颗粒,通过荧光染色分析和菌落形成实验,评估Ag_(2)Se纳米颗粒对P.gingivalis活性和克隆形成能力的影响;构建P.gingivalis感染的小鼠食管癌皮下荷瘤模型,通过RNAscope原位杂交和定量聚合酶链反应(qPCR)测定治疗后肿瘤组织中P.gingivalis的丰度,并监测荷瘤小鼠肿瘤体积的变化,以评估Ag_(2)Se纳米颗粒清除肿瘤组织中P.gingivalis后对小鼠食管癌恶性进展的影响。通过评估小鼠肝肾功能及主要脏器的病理变化,以评估Ag_(2)Se纳米颗粒的生物安全性。结果透射电子显微镜(TEM)的结果显示,本研究制备的Ag_(2)Se为直径50 nm左右的均匀分散球形纳米颗粒。体外实验结果表明Ag_(2)Se纳米颗粒能降低P.gingivalis的活力和克隆增殖能力,且随浓度的增加而逐渐增强(P<0.05)。体内实验结果证实,经Ag_(2)Se纳米颗粒治疗后,小鼠肿瘤组织中P.gingivalis的丰度降低、恶性增殖能力得到抑制(P<0.01)。治疗期间小鼠的肝肾功能和主要脏器未出现明显损伤,提示Ag_(2)Se纳米颗粒具有良好的生物相容性。结论Ag_(2)Se纳米颗粒对P.gingivalis具有显著的杀伤和抑制作用,在体内可有效清除胞内P.gingivalis,抑制食管癌的恶性进展,为食管癌的预防和治疗提供新的理论依据。Objectives To investigate the efficacy of Ag_(2)Se nanoparticles for eliminating intracellular Porphyromonas gingivalis(P.gingivalis)in esophageal cancer and examine the effect of P.gingivalis clearance on progression of esophageal cancer.Methods Ag_(2)Se nanoparticles were synthesized via a chemical synthesis method.The effects of Ag_(2)Se nanoparticles on P.gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays.In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P.gingivalis infection,the effect of treatment with Ag_(2)Se nanoparticles on the abundance of P.gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction(qPCR),and the changes in tumor volume were monitored.The biosafety of Ag_(2)Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice.Results Transmission electron microscopy revealed that the synthesized Ag_(2)Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm.In vitro experiments demonstrated that exposure to Ag_(2)Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P.gingivalis in a dose-dependent manner.In the tumor-bearing mice,treatment with Ag_(2)Se nanoparticles significantly reduced the abundance of P.gingivalis in tumor tissues and suppressed tumor cell proliferation.No significant damages to the liver and kidney functions or the major organs were observed in Ag_(2)Se nanoparticle-treated mice,demonstrating good biocompatibility of Ag_(2)Se nanoparticles.Conclusion Ag_(2)Se nanoparticles exhibit significant bactericidal and inhibitory effects against P.gingivalis,and can effectively eliminate intracellular P.gingivalis to suppress the growth of esophageal cancer allograft in mice,suggesting the potential of Ag_(2)Se nanoparticles in the treatment of esophageal cancer.

关 键 词：食管癌 牙龈卟啉单胞菌 纳米材料 酸响应性 

分 类 号：R73[医药卫生—肿瘤]