靶向肿瘤细胞的相变型纳米粒多模态显像及其声动力治疗的体外实验研究  

Tumor-targeting nanoparticles with phase transition for multimodal-imaging-guided sonodynamic therapy in vitro

作　　者：易衡静 张亮[2] 王志刚[2] 宋娇[2] 李雪霖[2] 王琦[3] 李兴升[1,2] YI Heng-jing;ZHANG Liang;WANG Zhi-gang;SONG Jiao;LI Xue-lin;WANG qi;LI Xing-sheng(Chongqing Key Laboratory of Ultrasound Molecular Imaging,Department of Geriatric,Chongqing 400010,China;Chongqing Key Laboratory of Ultrasound Molecular Imaging,Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China;Institute of Ultrasonic Engineering in Medical,Chongqing Medical University,ChongQing 400010,China)

机构地区：[1]重庆医科大学附属第二医院老年科,重庆400010 [2]重庆医科大学超声分子影像重庆市重点实验室,重庆400010 [3]重庆医科大学超声医学工程研究所,重庆400010

出　　处：《解放军医学杂志》2018年第10期822-827,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(31630026,81630047)

摘　　要：目的制备一种具有肿瘤靶向性的相变型多功能脂质纳米粒,探讨该纳米粒的体外多模态显像、寻靶和声动力治疗效果。方法采用乳化法制备包载IR780及全氟戊烷(PFP)的脂质纳米粒(Lip-PFP-IR780),检测纳米粒的基本特性。通过体外超声、光声、荧光成像评价多模态显像效果,通过共聚焦和流式细胞术评价其对4T1细胞(小鼠乳腺癌细胞)的寻靶能力,通过单线态氧(SOSG)检测法和细胞计数试剂盒(CCK-8法)评价其声动力治疗效果。结果制备的纳米粒大小均一,粒径为(338.5±124.2)nm,电位为(–27.6±2.4)mV,包封率为91.6%。纳米粒经低强度聚焦超声(LIFU)辐照相变后可用于超声造影显像;光声信号值呈浓度依赖性;荧光显像效果明显。4T1细胞对靶向纳米粒的结合率明显高于非靶向纳米粒(P<0.05)。纳米粒经LIFU辐照后,可以产生单线态氧,通过声动力杀伤肿瘤细胞,LIFU辐照组与未辐照组比较细胞存活率明显下降(P<0.05)。结论成功制备了靶向肿瘤细胞的相变型纳米粒Lip-PFP-IR780,能够进行多模态显像及声动力治疗。Objective To develop tumor-targeted multifunctional nanoparticles with phase transition,and to investigate their multimodal imaging,delivery efficiency on tumor cells and efficacy of sonodynamic therapy (SDT).Methods IR780 and perfluoropentane (PFP)based liposome (Lip-PFP-IR780)nanoparticles were synthesized by an emulsion strategy.The characteristics of these nanoparticles were determined.Multimodal imaging ability of Lip-PFP-IR780nanoparticles was evaluated by ultrasound (US),photoacoustic (PA)and fluorescence (FL)imaging in vitro.The delivery efficiency of Lip-PFP-IR780to 4T1 cancer cells (mouse breast cancer cells)was evaluated by the laser scanning confocal microscope and flow cytometry.In vitro sonodynamic properties of these nanoparticles was evaluated by Singlet Oxygen Sensor Green (SOSG)assay and CCK-8assay. Results These nanoparticles presented homogenized size distribution.The average diameter was 338.5±124.2nm and zeta potential was -27.6±2.4mV.Meanwhile,the entrapment efficiency of IR780was calculated as 91.6%.In vitro,after low intensity focused ultrasound (LIFU)radiation,the Lip-PFP-IR780nanoparticles undergone phase transformation and could be.used for US contrast imaging.The PA signal intensity of nanoparticles increased along with the increase of the concentrations.The nanoparticles also could be used for near-infrared fluorescence imaging in vitro.The binding efficiency of targeting nanoparticles in 4T1 cells was much higher than non-targeted nanoparticles (P<0.05).During SDT,it would cause cell death due to singlet oxygen (1O2) produced after the LIFU irradiation.As expected,the 4T1 tumor cells were ablated and the cell viability in LIFU irradiation groupssignificantly decreased compared with the groups without LIFU irradiation (P<0.05).Conclusion Tumor-targeted multifunctional nanoparticles with phase transition were successfully constructed for multimodal-imaging-guided SDT.

关 键 词：肿瘤靶向 相变 多模态显像 声动力治疗 

分 类 号：R73[医药卫生—肿瘤]