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基于DVDMS/IR780复合纳米粒抗肿瘤声动力实验研究
Preparation of sinoporphyrin sodium and IR780-based composite nanoparticles and its anti-tumor efficacy in sonodynamic therapy
- 第三军医大学学报 2021年43卷第7期 页码：606-613
- 作者机构：
1.1400010 重庆，重庆医科大学：附属第二医院核医学科
2.1400010 重庆，重庆医科大学：超声影像学研究所
- 作者简介：
[袁耿彪，E-mail：yuan-gb@126.com YUAN Gengbiao, E-mail: yuan-gb@126.com
- 基金信息：重庆市基础研究与前沿探索项目(CSTC2018jcyJA0389);重庆市技术创新与应用发展专项重点项目(CSTC2019jscx-dxwtBX0004)
DOI：10.16016/j.1000-5404.202011241
中图分类号： R454.3;R730.5;R944.9收稿：2020-11-25，
修回：2020-12-23，
纸质出版：2021-04-15
- 稿件说明：
移动端阅览
李倩茹, 郝兰, 王艺睿, 等. 基于DVDMS/IR780复合纳米粒抗肿瘤声动力实验研究[J]. 第三军医大学学报, 2021,43(7):606-613.
Qianru LI, Lan HAO, Yirui WANG, et al. Preparation of sinoporphyrin sodium and IR780-based composite nanoparticles and its anti-tumor efficacy in sonodynamic therapy[J]. Journal of Third Military Medical University, 2021, 43(7): 606-613.
李倩茹, 郝兰, 王艺睿, 等. 基于DVDMS/IR780复合纳米粒抗肿瘤声动力实验研究[J]. 第三军医大学学报, 2021,43(7):606-613. DOI： 10.16016/j.1000-5404.202011241.
Qianru LI, Lan HAO, Yirui WANG, et al. Preparation of sinoporphyrin sodium and IR780-based composite nanoparticles and its anti-tumor efficacy in sonodynamic therapy[J]. Journal of Third Military Medical University, 2021, 43(7): 606-613. DOI： 10.16016/j.1000-5404.202011241.
摘要
目的
2
制备一种搭载华卟啉钠（sinoporphyrin sodium，DVDMS）、IR780与全氟己烷（perfluorinated hexane，PFH）的聚乳酸-乙醇酸（poly lactic-co-glycolic acid，PLGA）肿瘤靶向多功能复合纳米粒（DIPP-NPs），评估其理化性质，探讨敏化剂DVDMS、IR780的协同增强声动力治疗（sonodynamic therapy，SDT）作用。
方法
2
用超声双乳化法制备DIPP-NPs，对其进行基本表征；采用光镜记录超声辐照前后纳米粒的变化；超声/光声成像系统评价其体外成像能力；激光共聚焦显微镜评价PP-NPs、DPP-NPs、IPP-NPs、DIPP-NPs 4种纳米粒对4T1乳腺癌细胞的体外
靶向能力；单线态氧检测法（singlet oxygen sensor green reagent
SOSG）评价其体外活性氧产量；CCK-8法评价其细胞毒性；将4T1乳腺癌细胞分为阴性对照组、仅US组、仅DIPP-NPs组、DPP-NPs+US组、IPP-NPs+US组、DIPP-NPs+US组（
n
=3），通过CCK-8法检测各组细胞存活率来评价其体外SDT效果；建立4T1乳腺癌荷瘤鼠模型并分为阴性对照组、仅US组、仅DIPP-NPs组、DPP-NPs+US组、IPP-NPs+US组、DIPP-NPs+US组（
n
=3），通过测量各组荷瘤鼠肿瘤体积/质量，计算肿瘤体积/质量抑制率来评价其体内SDT效果。
结果
2
成功制备DIPP-NPs，不同显微镜下观察呈圆球形，大小均一，粒径（341.17±16.97）nm，电位（-12.77±0.88）mV，DVDMS、IR780的包封率分别为（92.84±1.58）%、（96.57±1.48）%；DIPP-NPs经超声辐照后发生相变，光镜下观察到其直径随辐照时间延长而增大，体外超声成像显示其回声强度随辐照时间延长而增强；体外光声成像显示其光声信号随纳米粒浓度升高而增强；激光共聚焦显微镜观察到DIPP-NPs组中4T1细胞周围的纳米粒明显多于其他3组；SOSG体外活性氧检测结果发现DIPP-NPs的活性氧产量随辐照时间延长而增加；CCK-8细胞毒性检测结果显示不同浓度DIPP-NPs未见明显细胞毒性；体外SDT结果显示DIPP-NPs+US组的细胞存活率为（56.04±2.28）%，明显低于DPP-NPs+US组[（76.83±1.52）%
]
、IPP-NPs+US组[（74.03±2.64）%
]
，差异具有统计学意义（
P
<
0.05）；体内SDT实验结果显示DIPP-NPs+US组的肿瘤体积/质量抑制率为（73.28±1.58）% /（75.76±3.49）%，明显高于DPP-NPs+US组[（46.93±4.41）%/（43.50±2.27）%
]
与IPP-NPs+US组[（47.44±1.27）%/（44.87±4.30）%
]
，差异具有统计学意义（
P
<
0.05）。
结论
2
成功制备肿瘤靶向多功能复合纳米粒DIPP-NPs，其具有良好的协同增强SDT作用。
Abstract
Objective
2
To prepare the tumor targeting multifunctional composite nanoparticles (DIPP-NPs) by encapsulating sinoporphyrin sodium (DVDMS)
IR780 and perfluorinated hexane (PFH)
evaluate their physicochemical properties
and explore the synergistic enhancement of sonodynamic therapy (SDT) between DVDMS and IR780.
Objective
2
DIPP-NPs were synthesized
via
double emulsion and then characterized. The changes of nanoparticles before and after ultrasonic irradiation were observed by optical microscopy. Ultrasonic and photoacoustic imaging systems were used to evaluate the imaging capability
in vitro
. Targeting ability
in vitro
was evaluated by confocal laser scanning microscopy. The production of reactive oxygen species (ROS) was demonstrated by sing
let oxygen detection (SOSG). CCK-8 assay was used to detect the cytotoxicity and synergistic enhancement of SDT in murine mammary carcinoma cell line 4T1. The synergistic enhancement of SDT in 4T1 xenograft mouse model was evaluated by measuring tumor volume and weight to calculate the inhibitory rates.
Results
2
DIPP-NPs were successfully prepared
as uniform round-shaped particles
341.17±16.97 nm in diameter and -12.77±0.88 mV in Zeta potential. The encapsulation rate of DVDMS and IR780 was (92.84±1.58) % and (96.57±1.48) %
respectively. After irradiated with ultrasonic
DIPP-NPs were getting bigger and bigger in diameter under a optical microscope. Meanwhile
ultrasound imaging results showed that the ultrasound signals were enhanced with prolonged irradiation time. In addition
photoacoustic imaging results showed that the photoacoustic signal intensity was increased with the increment of nanoparticle concentration. Laser confocal microscopy demonstrated that there were more nanoparticles around 4T1 cells in DPP-NPs
IPP-NPs and DIPP-NPs groups than in PP-NPs group. SOSG detection results showed that the production of ROS was gradually increased with prolonged irradiation time. CCK-8 assay indicated that there was no obvious cytotoxicity of the nanoparticles and the cell viability in DIPP-NPS+US group was (56.04±2.28)%
which was obviously lower than that in DPP-NPS+US [(76.83±1.52)%
]
and IPP-NPS +US groups [(74.03±2.64)%
both
P
<
0.05
]
. Xenograft experiment showed that the inhibitory rate was (73.28±.58)% for tumor volume
and (75.76±3.49)% in weight in DIPP-NPS+US group
which were significantly higher than those in DPP-NPS+US [(46.93±4.41)%
(43.50±2.27)%
]
and the IPP-NPS+US groups [(47.44±1.27)%
(44.87±4.30)%
P
<
0.05
]
.
Conclusion
2
The tumor-targeting multifunctional composite nanoparticles DIPP-NPs are successfully prepared
which have a good synergistic enhancement of SDT effectiveness.
关键词
Keywords
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