一种磷脂包覆氯化钠微纳米粒子肿瘤治疗探针制备及^(23)Na-MRI初步实验研究  

A Phospholipid-Coated Sodium Chloride Nanoparticle Tumor Therapeutic Probe Preparation and Preliminary ^(23)Na-MRI Study

作　　者：田乃月 孙维鑫 张鑫锋 杨乔乔 王凯[1,2] TIAN Nai-yue;SUN Wei-xin;ZHANG Xin-feng;YANG Qiao-qiao;WANG Kai(Department of Nuclear Medicine,The Fourth Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang,150000,China;Department of TOF-PET/CT/MR Center,The Fourth Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang,150000,China)

机构地区：[1]哈尔滨医科大学附属第四医院核医学科,黑龙江哈尔滨150000 [2]哈尔滨医科大学附属第四医院TOF-PET/CT/MR中心,黑龙江哈尔滨150000

出　　处：《现代生物医学进展》2025年第4期612-621,共10页Progress in Modern Biomedicine

基　　金：国家自然科学基金重大科研仪器项目(81627901);黑龙江省自然科学基金项目(LH2020H067)。

摘　　要：目的:制备和表征磷脂包覆氯化钠微纳米粒子(PSCNPs)探针及其^(23)Na-MR活体成像效果.方法:采用非水反相微乳液法制备PSCNPs,并通过透射电子显微镜(SEM、TEM)、X射线衍射(XRD)、动态光散射(DLS)等方法对其形貌、粒径、元素组成等特性进行表征;在细胞水平,检测PSCNPs对乳腺癌(4T1)和肺癌(H460、A549)的细胞毒性;在活体动物上,应用PSCNPs进行4T1荷瘤小鼠乳腺癌治疗,通过^(23)Na-MRI实时监测治疗效果.结果:制备了形态均一、粒径分布均匀的PSCNPs,DLS结果显示粒径为1156 nm,且XRD分析确认了PSCNPs晶体结构.在细胞毒性实验中,PSCNPs对乳腺癌和肺癌细胞均展现出剂量依赖性毒性作用,即当PSCNPs浓度达到320μg/mL时,细胞存活率下降至12%-33%.在4T1小鼠乳腺癌模型中,PSCNPs显著抑制肿瘤生长.与对照组相比,治疗组肿瘤体积平均减少了60%,差异具有统计学意义(P<0.05).^(23)Na-MRI成像技术能够清晰、直观地监测到PSCNPs在肿瘤区域的积聚情况以及治疗引起的钠离子浓度变化,为肿瘤治疗效果提供了可靠的实时评估手段.结论:成功制备了可^(23)Na-MRI成像的磷脂包覆氯化钠微纳米粒子肿瘤治疗探针.Objective:To prepare and characterize phospholipid-coated sodium chloride micro-nanoparticles(PSCNPs)and evaluate their effects in vivo imaging using ^(23)Na magnetic resonance(MR).Methods:PSCNPs were synthesized via a non-aqueous reverse microemulsion method.Their morphology,particle size,elemental composition,and other properties were characterized using scanning electron microscopy(SEM),transmission electron microscopy(TEM),X-ray diffraction(XRD),and dynamic light scattering(DLS).The cytotoxicity of PSCNPs was assessed in breast cancer(4T1)and lung cancer(H460,A549)cell lines.In vivo,PSCNPs were administered to a 4T1 mouse breast cancer model,and their therapeutic efficacy was monitored in real-time using ^(23)Na-MR imaging.Results:PSCNPs with homogeneous morphology and uniform particle size distribution were successfully synthesized.DLS analysis revealed a particle size of 1156 nm,and XRD confirmed their crystal structure.Cytotoxicity studies showed that PSCNPs exerted a dose-dependent toxic effect on both breast and lung cancer cells,reducing cell viability to 12%-33%at a concentration of 320μg/mL.In the 4T1 mouse breast cancer model,PSCNPs significantly inhibited tumor growth,with an average tumor volume reduction of 60%in the treatment group compared to the control group,a difference that was statistically significant(P<0.05).^(23)Na-MRI provided a reliable real-time method for assessing the therapeutic efficacy by visually monitoring the accumulation of PSCNPs in the tumor region and the associated changes in sodium ion concentration.Conclusion:Successful preparation of phospholipid-coated sodium chloride micro-nanoparticle tumor therapeutic probes for ^(23)Na-MRI.

关 键 词：磷脂包覆氯化钠微纳米粒子 钠磁共振成像 肿瘤精准治疗 非水反相微乳液法 

分 类 号：R3[医药卫生—基础医学] R453.9