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癌细胞膜靶向相变纳米分子探针研制及光声/超声双模态显像与光热治疗乳腺癌 被引量:6

Biomimetic Phase Transition Nanoprobes of Cancer Cell Membrane and Dual Mode Imaging and Photothermal Therapy for Breast Cancer
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摘要 目的制备一种癌细胞膜包被的相变纳米分子探针,观察其体外光声/超声双模态成像效果,并探讨其靶向同源乳腺癌细胞的能力及光热治疗(PTT)杀伤效果。材料与方法通过化学裂解和反复冻融提取乳腺癌4T1细胞膜(CCM),然后以双乳化法联合膜挤压法制备CCM包被的同时携载全氟戊烷(PFP)和Fe_(3)O_(4)的聚乳酸-羟基乙酸共聚物(PLGA)相变分子探针(CPFP-NPs);考察CPFP-NPs基本表征,并研究其同源靶向乳腺癌细胞、光声成像及液气相变增强超声显像的能力;观察CPFPNPs在不同浓度及不同功率激光辐照时的光热性能;以AM/PI活死细胞染色法和流式细胞术评估其对乳腺癌细胞的PTT杀伤效果。结果成功制备纳米探针CPFP-NPs,呈球形“壳核”结构,大小均一,平均粒径为(237.17±2.60)nm,表面电位为(-19.50±0.27)mV;激光共聚焦显微镜下观察,纳米探针可靶向同源4T1细胞(靶向结合率达92.01%);CPFP-NPs在体外可增强光声成像,光声信号随纳米粒浓度升高而增强,经激光辐照后,CPFP-NPs发生相变并增强超声成像。CPFP-NPs联合激光辐照,对4T1细胞具有明显的光热杀伤效应,细胞凋亡率高达95.97%。结论研制了一种乳腺癌细胞膜包被的光声/超声双模态相变分子探针,该探针具有良好的靶向同源肿瘤的能力,并可以显著增强肿瘤双模态显像及PTT效果。 Purpose To prepare a biomimetic nanoprobe,to observe its US/PA dual mode imaging effect,and to explore its possibility for targeting homologous breast cancer cells and photothermal therapy in vitro.Materials and Methods The cell membrane of breast cancer 4T1 was extracted by chemical cleavage and repeated freezing and thawing.The polylactic acid-glycolic acid copolymer biomimetic nanoprobe loaded with iron oxide nanoparticles(Fe_(3)O_(4))and phase-shift material perfluoropentane(PFP)was prepared by double emulsification and extrusion.The basic characteristics of nanoprobe,the ability of liquid-gas phase transition,the photoacoustic and the ultrasonic imaging effects were detected.And the photothermal property of the nanoprobe was assessed.AM/PI double staining and flow cytometry were used to evaluate the effect of photothermal therapy in vitro.Results The nanoprobe(CPFP-NPs)was prepared successfully,and spherical“core-shell structure”in shape and uniform in size,in a particle size of(237.17±2.60)nm,at a surface potential of(-19.50±0.27)mV.It was verified that CPFP-NPs could active target homologous 4T1 cells under laser confocal microscopy(targeted binding rate was 92.01%).The photoacoustic signal of nanoprobe was also enhanced with the enhancement of its concentration.The ultrasonic echo intensity was obviously enhanced after Laser irradiates nanoprobes.In vitro apoptosis experiments showed that the nanoprobe had the ability to significantly enhance the effect of photothermal therapy(the apoptotic rate was 95.97%).Conclusion A biomimetic phase transition molecular probe of breast cancer cell membrane preparation has been developed,which has the ability of ultrasonic/photoacoustic dual mode imaging,providing a new method and new idea for early diagnosis and treatment of breast cancer.
作者 唐芮 胡雅琴 何红叶 林晓红 万莉 李攀 TANG Rui;HU Yaqin;HE Hongye;LIN Xiaohong;WAN Li;LI Pan(Department of Ultrasound,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China;Institute of Ultrasound Imaging,Chongqing Medical University,Chongqing 400010,China;不详)
出处 《中国医学影像学杂志》 CSCD 北大核心 2022年第1期1-7,共7页 Chinese Journal of Medical Imaging
基金 国家自然科学基金面上项目(81971633) 重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0220) 重庆市教委科学技术研究项目(KJZD-K201900401)。
关键词 癌细胞膜 分子探针 液气相变 双模态成像 光热治疗 超声检查 乳腺肿瘤 Cancer cell membrane Nanometer molecular probe Liquid-gas phase transition Dual mode imaging Photothermal therapy Ultrasonography Breast neoplasms
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