脂质纳米颗粒共载miR-145/CPT肝癌靶向共递送及磁共振成像的初步研究  

Co-loaded with miR-145/CPT nanoparticles for targeted delivery and magnetic resonance imaging in hepatocellular carcinoma

作　　者：容静 刘彤彤 尹秀娟 张磊[2] 王啸[1] Rong Jing;Liu Tongtong;Yin Xiujuan;Zhang Lei;Wang Xiao(Dept of Radiology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;School of Pharmacy,Anhui Medical University,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province,Hefei 230032)

机构地区：[1]安徽医科大学第一附属医院放射科,合肥230022 [2]安徽医科大学药学院炎症免疫性疾病安徽省实验室,合肥230032

出　　处：《安徽医科大学学报》2024年第9期1501-1508,共8页Acta Universitatis Medicinalis Anhui

基　　金：安徽省高校自然科学研究项目(编号:2023AH040370);安徽医科大学科研水平提升计划(编号:2021xkjT015)。

摘　　要：目的制备肝癌靶向脂质纳米颗粒(LA-CMGL)共载miR-145/喜树碱(CPT),评估其靶向性、联合抗肿瘤作用及磁共振成像效果。方法采用激光共聚焦显微镜和流式细胞术评估HepG2细胞和HepaRG细胞对乳糖酸修饰和未修饰脂质纳米颗粒的靶向摄取情况;实时荧光定量(qPCR)评估肿瘤细胞和肿瘤组织内miR-145含量;采用CCK-8法检测CPT、LA-CPT-LNPs、LA-CMGL对HepG2细胞的细胞毒性;采用qPCR评估CPT、LA-CPT-LNPs、LA-CMGL对HepG2细胞凋亡的影响;采用磁共振成像(MRI)测定LA-CMGL的弛豫率,评估其肝癌细胞靶向成像效果。结果HepG2细胞对LA-CMGL的摄取率明显大于CMGL;LA-CMGL组肝癌细胞和小鼠肝癌组织内miR-145的相对含量显著高于游离miR-145和CMGL组(P<0.001);LA-CMGL组对HepG2细胞的凋亡率高于CMGL组和CPT组(P<0.01);在相同钆离子(Gd 3+)浓度下,LA-CMGL的弛豫率显著高于Gd-DOTA,且LA-CMGL在HepG2细胞内的MRI信号相比CMGL及Gd-DOTA显著增高。结论LA-CMGL有良好的肝癌靶向递送、联合抗肿瘤和磁共振肝癌靶向成像效果,为药物/基因联合治疗肝癌提供了新思路。Objective To develop liver cancer-targeted nanoparticles(LA-CMGL)co-loaded with miR-145/camptothecin(CPT)and assess their targeting specificity,combined anti-tumor effects,and magnetic resonance imaging efficacy.Methods Laser scanning confocal microscopy and flow cytometry were utilized to evaluate the targeted uptake of lactobionic acid-modified and unmodified nanoparticles by HepG2 cells and HepaRG cells;quantitative polymerase chain reaction(qPCR)was employed to assess miR-145 content in tumor cells and tissues.The cytotoxicity of CPT,LA-CPT-LNPs and LA-CMGL on HepG2 cells were assessed using the CCK-8 assay.qPCR was also used to evaluate the effect of CPT,LA-CPT-LNPs and LA-CMGL on apoptosis of HepG2 cells.MRI was performed to measure the relaxation rate of LA-CMGL and evaluate its targeting imaging effect on liver cancer cells.Results The uptake rate of LA-CMGL by HepG2 cells surpassed that of CMGL significantly.The relative miR-145 content in liver cancer cells and mouse liver cancer tissues in the LA-CMGL group was markedly higher compared to free miR-145 and CMGL groups(P<0.001).The apoptosis rate of HepG2 cells in the LA-CMGL group exceeded that in the CMGL group and CPT group(P<0.01).At the same Gd 3+concentration,the relaxation rate of LA-CMGL significantly surpassed that of Gd-DOTA,and the MRI signal of LA-CMGL in HepG2 cells markedly increased compared to CMGL and Gd-DOTA.Conclusion LA-CMGL exhibits promising liver cancer-targeted delivery,combined anti-tumor effects,and MRI liver cancer cell-targeted imaging,offering a novel avenue for combined drug/gene therapy for liver cancer.

关 键 词：磁共振成像 脂质纳米颗粒 原发性肝癌 分子靶向治疗 乳糖酸 MIR-145 喜树碱 联合治疗 

分 类 号：R445.2[医药卫生—影像医学与核医学] R735.7[医药卫生—诊断学]