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超声可视化的肿瘤原位液固相变生物磁铁聚集磁性脂质体的实验研究
Tumor-specific aggregation of magnetic liposome nanoparticles in tumor-bearing mice after ultrasound-guided intratumor injection of liquid-solid phase-change biomagnetic material
- 第三军医大学学报 2020年42卷第20期 页码：1995-2002
- 作者机构：
1.400016 重庆，重庆医科大学超声影像学研究所，超声分子影像重庆市重点实验室
2.200025 上海，上海交通大学医学院附属瑞金医院超声科
3.400010 重庆，重庆医科大学第二附属医院超声科
4.200233 上海，上海交通大学附属第六人民医院超声科，上海超声医学研究所
- 作者简介：
[郑元义，E-mail: zhengyuanyi@163.com ZHENG Yuanyi, E-mail: zhengyuanyi@163.com
- 基金信息：国家自然科学基金国际(地区)合作与交流项目(81720108023);国家自然科学基金青年科学基金(81801699)
DOI：10.16016/j.1000-5404.202004297
中图分类号： R445.1;R737.9;R944.9收稿：2020-04-28，
修回：2020-07-29，
纸质出版：2020-10-30
- 稿件说明：
移动端阅览
郝俊年, 汪蓉晖, 冉海涛, 等. 超声可视化的肿瘤原位液固相变生物磁铁聚集磁性脂质体的实验研究[J]. 第三军医大学学报, 2020,42(20):1995-2002.
Junnian HAO, Ronghui WANG, Haitao RAN, et al. Tumor-specific aggregation of magnetic liposome nanoparticles in tumor-bearing mice after ultrasound-guided intratumor injection of liquid-solid phase-change biomagnetic material[J]. Journal of Third Military Medical University, 2020, 42(20): 1995-2002.
郝俊年, 汪蓉晖, 冉海涛, 等. 超声可视化的肿瘤原位液固相变生物磁铁聚集磁性脂质体的实验研究[J]. 第三军医大学学报, 2020,42(20):1995-2002. DOI： 10.16016/j.1000-5404.202004297.
Junnian HAO, Ronghui WANG, Haitao RAN, et al. Tumor-specific aggregation of magnetic liposome nanoparticles in tumor-bearing mice after ultrasound-guided intratumor injection of liquid-solid phase-change biomagnetic material[J]. Journal of Third Military Medical University, 2020, 42(20): 1995-2002. DOI： 10.16016/j.1000-5404.202004297.
摘要
目的
2
构建超声监控下肿瘤原位液固相变钕铁硼生物磁铁(NdFeB/Fe
3
O
4
/PLGA，NFP)，研究静脉注射型磁性脂质体纳米粒(magnetic liposome nanoparticles
MLPs)在肿瘤内富集的可行性及效率。
方法
2
制备液固相变NFP生物磁铁，对其液固相变能力、形态和充磁磁化能力等进行表征。同时制备包载超顺磁性Fe
3
O
4
的脂质体纳米粒，表征其形态、大小及粒径等一般性能。通过细胞毒性增殖实验检测NFP生物磁铁和MLPs的细胞生物安全性。通过体外循环模拟捕获实验检测在微循环的流速下NFP对血管中MLPs的捕获效率。通过建立4T1乳腺癌荷瘤小鼠模型
探索超声监控下注射NFP可磁化的生物磁铁植入体作为体内生物磁铁靶向吸引尾静脉注射连接荧光染料的MLPs的能力。
结果
2
扫描电镜与元素分析结果显示相变后的植入体各元素分布均匀。体外充磁实验证实NFP生物磁铁充磁后被赋予磁性，25、50、75、100 μL NFP生物磁铁的磁力分别为(350.14±23.89)、(493.47±19.54)、(679.39±34.23)、(812.36±27.99) Gs，结果显示NFP生物磁铁的磁性随体积增大而增强。成功制备磁性脂质体纳米粒，透射电镜观察呈球形，大小较均匀，粒径为(373.658±50.000)nm，电位为(-24.8±1.4)mV。细胞毒性实验显示NFP生物磁铁和MLPs对肿瘤细胞和正常细胞均未见明显的生长抑制作用。体内的荧光成像结果显示NFP生物磁铁与MLPs联合使用组肿瘤部位的荧光明显增强，其余各组肿瘤部位未见明显增强。
结论
2
成功制备了超声可视化液固相变植入体NFP及生物安全性较好的MLPs
该植入体磁化后可在肿瘤原位产生磁场，吸引经尾静脉注射的MLPs特异性地富集于肿瘤。
Abstract
Objective
2
To prepare ultrasound-guided intratumor injection of liquid-solid phase-transition biomagnetic material (NdFeB/Fe
3
O
4
/PLGA
NFP) and investigate its feasibility and efficiency of aggregating for targeted aggregation of intravenously injected magnetic liposome nanoparticles (MLPs).
Methods
2
The biomagnetic material NFP was prepared and its liquid-solid phase transition ability
morphology and magnetization performances were assessed; the form
particle size and diameter of MLPs were also characterized. The biocompatibility of NFP and MLPs were evaluated by cytotoxic proliferation experiments
and the efficiency of MLP capture by NFP was determined using an
in vitro
model of extracorporeal circulation. A 4T1 mouse model bearing breast cancer xenograft was established
in which NFP was injected in the tumor under ultrasound guidance and MLPs conjugated with a fluorescent dye was injected intr
avenously by tail vein. The efficiency of NFP implant for capturing the MLPs for targeted aggregation of the latter in the xenograft was evaluated using
in vivo
fluorescence imaging.
Results
2
The biomagnetic material NFP capable of liquid-solid phase transition was successfully prepared. Scanning electron microscopy and elemental mapping results showed a homogeneous distribution of the elements in NFP after phase transition. The NFP implant could be efficiently magnetized
in vitro
and the magnetic forces of NFP was positively correlated with its volume (350.14±23.89
493.47±19.54
679.39±34.23
and 812.36±27.99 Gs for 25
50
75
and 100 μL of NFP
respectively). The prepared MBLs had a uniform particle size of 373.658±50.000 nm with a zeta potential of -24.8±2.5 mV. Cytotoxicity experiments with tumor cells and normal cells showed no obvious cytotoxicity of either NFP or MLPs.
in vivo
fluorescence imaging showed that following intravenous MLB injection and intratumor NFP implantation
the fluorescence intensity was significantly enhanced in the xenografts in the tumor-bearing mice.
Conclusion
2
The prepared liquid-solid phase-change biomagnetic NFP and the MLPs have good biocompatibility. NFP implantation in the tumor can efficiently capture intravenously injected MLPs to achieve targeted aggregation of MLPs in the tumors.
关键词
Keywords
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