Ultrasound imaging and photothermal therapy of ZnPc loaded angiogenesis-targeting nanoparticles <italic style="font-style: italic">in vitro</italic>

Yuli CHEN; Fengqiu LIU; Yuan GUO; Tao YU; Zhigang WANG; Haitao RAN; Yang CAO

doi:10.16016/j.1000-5404.201711068

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Ultrasound imaging and photothermal therapy of ZnPc loaded angiogenesis-targeting nanoparticles in vitro

Basic Medicine | 更新时间：2026-01-09

- Ultrasound imaging and photothermal therapy of ZnPc loaded angiogenesis-targeting nanoparticles in vitro
- Journal of Third Military Medical University Vol. 40, Issue 9, Pages: 761-767(2018)
- 作者机构：
  
  1.400010 重庆, 超声分子影像重庆市重点实验室
  2.402360 重庆, 重庆市大足区人民医院超声科
  3.400010 重庆, 重庆医科大学附属第二医院超声科
- 作者简介：
- 基金信息：
  
  the Key Program of National Natural Science Foundation of China(81630047);the General Program of National Natural Science Foundation of China(81471713)
- DOI：10.16016/j.1000-5404.201711068
  CLC： R445.1;R944.9;R981
- Received：15 November 2017，
  
  Revised：2018-01-25，
  
  Published：15 May 2018
- 稿件说明：
移动端阅览
Yuli CHEN, Fengqiu LIU, Yuan GUO, et al. Ultrasound imaging and photothermal therapy of ZnPc loaded angiogenesis-targeting nanoparticles in vitro[J]. Journal of Third Military Medical University, 2018, 40(9): 761-767.
DOI：

Yuli CHEN, Fengqiu LIU, Yuan GUO, et al. Ultrasound imaging and photothermal therapy of ZnPc loaded angiogenesis-targeting nanoparticles in vitro[J]. Journal of Third Military Medical University, 2018, 40(9): 761-767. DOI： 10.16016/j.1000-5404.201711068.

摘要

目的

制备一种新型靶向新生血管诊疗一体化的超声分子探针

体外评价其靶向性、增强超声显像及光热治疗能力。

方法

采用双乳化法制备搭载全氟己烷(perfluorohexane

PFH)和酞菁锌(zinc phthalocyanine

ZnPc)的PLGA纳米粒; 用碳二亚胺法将纳米粒与血管内皮生长因子受体-2(vascular endothelial growth factor receptor-2

VEGFR-2)抗体相偶联制备靶向纳米粒; 检测其一般特性、体外寻靶能力; 经激光辐照后检测其增强超声显像以及光热治疗能力。

结果

成功制备出靶向纳米粒

粒径(256.40±57.14)nm; CCK-8检测结果表明纳米粒没有明显的细胞毒性(

=0.402

=0.837);激光共聚焦显微镜及流式细胞仪结果均证明靶向纳米粒具有良好的靶向能力

流式细胞仪检测非靶向组、抗体封闭组、靶向组中

纳米粒与细胞连接率分别为(9.52±2.14)%、(9.92±1.62)%、(61.89±3.62)%

差异有统计学意义(

=463.7

0.05)

非靶向组(

=40.21

0.05)、抗体封闭组(

=30.91

0.05)分别与靶向组比较差异有统计学意义。经激光(1 W/cm

5 min)辐照后纳米粒能够发生相变

增强超声显像并能使局部温度升高超过42 ℃

对细胞具备光热治疗的能力

而靶向组诱导细胞凋亡比例[(79.49±2.22)%

]

明显高于非靶向组[(24.23±1.95)%

0.05

]

。

结论

成功制备了靶向新生血管诊疗一体化超声分子探针

其具有良好的靶向能力

可用于增强超声显像及光热治疗。

Abstract

Objective

To prepare a new type of angiogenesis-targeting theranostic molecular probe and investigate its targeting ability

contrast enhanced ultrasound imaging and photothermal therapy

in vitro

Methods

Perfluorohexane (PFH) and zinc phthalocyanine (ZnPc) loaded targeting nanoparticles were prepared by double emulsification method and conjugated with vascular growth factor receptor-2 (VEGFR-2) antibodies

via

carbodiimide technique.The basic features and targeting ability of nanoparticles were detected.Contrast enhanced ultrasound imaging was observed and cell apoptosis was detected after laser irradiation.

Results

Targeting nanoparticles were successfully prepared with an average diameter of 256.40±57.14 nm.No obvious cytotoxicity was observed by CCK-8 assay (

=0.402

0.05).Good targeting ability was observed by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM).FCM results showed that the connection rate was (9.52±2.14)%

(9.92±1.62)%

and (61.89±3.62)% respectively

in the un-targeting group

closed receptor group

and targeting group

with significant difference (

=463.7

0.05).And significant differences were also seen in the un-targeting group (

=40.21

0.05) and the closed receptor group (

=30.91

0.05) when compared with the targeting group.After laser irradiation (1 W/cm

5 min)

phase transition of PFH was excited

which resulting in contrast enhanced ultrasound imaging and regional temperature exceeding 42 ℃

and thus leading to photothermal ability.The apoptotic rate was significantly higher in the targeting group than the un-targeting group [(79.49±2.22)%

(24.23±1.95)%

0.05

]

Conclusion

PFH and ZnPc loaded targeting nanoparticles are successfully prepared

which show strongly specific affinity to VEGFR-2.The novel nanoparticles show a great potential to be used for ultrasound imaging and photothermal therapy.

关键词

Keywords

references

CAVALLI R, SOSTER M, ARGENZIANO M.Nanobubbles:a promising efficienft tool for therapeutic delivery[J].Therap Deliv, 2016, 7(2):117-138.DOI:10.4155/tde.15.92.

GVVENER N, APPOLD L, DE LORENZI F, et al .Recent advances in ultrasound-based diagnosis and therapy with micro-and nanometer-sized formulations[J ] .Methods, 2017, 130(2017):4-13.DOI:10.1016/j.ymeth.2017.05.018.

王志刚.超声分子成像研究进展[J].中国医学影像技术, 2014, 30(8):1125-1126.DOI:10.13929/j.1003-3289.2014.08.001.

WANG Z G.Progresses of ultrasound molecular imaging[J].Chin J Med Imaging Technol, 2014, 30(8):1125-1126.DOI:10.13929/j.1003-3289.2014.08.001.

王运来.超声造影的临床应用与前景[J].中医药管理杂志, 2015, 23(17):149-150.DOI:10.16690/j.cnki.1007-9203.2015.17.154.

WANG Y L.Clinical application and prospect of contrast-enhanced ultrasound[J].J Tradi Chin Med Manag, 2015, 23(17):149-150.DOI:10.16690/j.cnki.1007-9203.2015.17.154.

CAMARÉ C, PUCELLE M, NÈGRE-SALVAYRE A, et al .Angiogenesis in the atherosclerotic plaque[J ] .Redox Biol, 2017, 12:18-34.DOI:10.1016/j.redox.2017.01.007.

RUDDY J M, IKONOMIDIS J S, JONES J A.Multidimensional contribution of matrix metalloproteinases to atherosclerotic plaque vulnerability:multiple mechanisms of inhibition to promote stability[J].J Vasc Res, 2016, 53(1/2):1-16.DOI:10.1159/000446703.

RAMJIAWAN R R, GRIFFIOEN A W, DUDA D G.Anti-angiogenesis for cancer revisited:is there a role for combinations with immunotherapy?[J].Angiogenesis, 2017, 20(2):185-204.DOI:10.1007/s10456-017-9552-y.

GREENBERG D A, JIN K.Vascular endothelial growth factors (VEGFs) and stroke[J].Cell Mol Life Sci, 2013, 70(10):1753-1761.DOI:10.1007/s00018-013-1282-8.

HSU J Y, WAKELEE H A.Monoclonal antibodies targeting vascular endothelial growth factor[J].Biodrugs, 2009, 23(5):289-304.DOI:10.2165/11317600-000000000-00000.

SHANNON A M, BOUCHIERHAYES D J, CONDRON C M, et al .Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies[J ] .Cancer Treat Rev, 2003, 29(4):297-307.

KHAN I, GOTHWAL A, SHARMA A K, et al .PLGA nanoparticles and their versatile role in anticancer drug delivery[J ] .Crit Rev Ther Drug Carrier Syst, 2016, 33(2):159-193.DOI:10.1615/CritRevTherDrugCarrierSyst.2016015273.

RAPOPORT N.Drug-loaded perfluorocarbon nanodroplets for ultrasound-mediated drug delivery[J].Adv Exp Med Biol, 2016, 880:221-241.DOI:10.1007/978-3-319-22536-4_13.

WINTER P M.Perfluorocarbon nanoparticles:evolution of a multimodality and multifunctional imaging agent[J].Scientifica (Cairo), 2014, 2014:746574.DOI:10.1155/2014/746574.

BAN Q, BAI T, DUAN X, et al .Noninvasive photothermal cancer therapy nanoplatforms via integrating nanomaterials and functional polymers[J ] .Biomater Sci, 2017, 5(2):190-210. DOI:10.1039/c6bm00600k.

CHEN Q, WEN J, LI H, et al .Recent advances in different modal imaging-guided photothermal therapy[J ] .Biomaterials, 2016, 106:144-166.DOI:10.1016/j.biomaterials.2016.08.022.

肖洋, 冉海涛, 夏琼, 等.靶向VEGFR-2光声/超声双模态造影剂的制备及体外寻靶实验研究[J].中国介入影像与治疗学, 2015, 12(9):554-558.DOI:10.13929/J.1672-8475.2015.09.009.

XIAO Y, RAN H T, XIA Q, et al .Preparation of VEGFR-2 targeted photoacoustic/ultrasound dual mode contrast agent and its targeting study in vitro [J ] .Chin J Interv Imaging Ther, 2015, 12(9):554-558.DOI:10.13929/J.1672-8475.2015.09.009..

宣吉晴, 陈瑜莉, 敖梦, 等.携带cRGD肽的靶向纳米粒超声造影剂的制备以及体外寻靶实验研究[J].中国医学影像技术, 2017, 33(6):811-815.DOI:10.13929/j.1003-3289.201702043.

XUAN J Q, CHEN Y L, AO M, et al .Experimental study on preparation and targeting research in vitro of targeted nanoparticle ultrasound contrast agent carrying cRGD[J ] .Chin J Med Imaging Technol, 2017, 33(6):811-815.DOI:10.13929/j.1003-3289.2017 02043..

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Ultrasound imaging and photothermal therapy of ZnPc loaded angiogenesis-targeting nanoparticles in vitro

DOI：10.16016/j.1000-5404.201711068

摘要

Abstract

关键词

Keywords

references