Effect of sound sensitive nano-liposomes combined with low intensity focused ultrasound on proliferation of HepG2 cells and its CT imaging <italic style="font-style: italic">in vitro</italic>

Dan GUO; Xingyue WANG; Mixiao TAN; Mingzhu LIU; Hantao RAN; Zhigang WANG

doi:10.16016/j.1000-5404.201806153

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Effect of sound sensitive nano-liposomes combined with low intensity focused ultrasound on proliferation of HepG2 cells and its CT imaging in vitro

Basic Medicine | 更新时间：2026-01-09

- Effect of sound sensitive nano-liposomes combined with low intensity focused ultrasound on proliferation of HepG2 cells and its CT imaging in vitro
- Journal of Third Military Medical University Vol. 40, Issue 23, Pages: 2180-2189(2018)
- 作者机构：
  
  1.400016 重庆, 重庆医科大学超声分子影像重庆市重点实验室
  2.400010 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)
- DOI：10.16016/j.1000-5404.201806153
  CLC： R454.3;R73-36;R944.9
- Received：23 June 2018，
  
  Revised：2018-08-03，
  
  Published：15 December 2018
- 稿件说明：
移动端阅览
Dan GUO, Xingyue WANG, Mixiao TAN, et al. Effect of sound sensitive nano-liposomes combined with low intensity focused ultrasound on proliferation of HepG2 cells and its CT imaging in vitro[J]. Journal of Third Military Medical University, 2018, 40(23): 2180-2189.
DOI：

Dan GUO, Xingyue WANG, Mixiao TAN, et al. Effect of sound sensitive nano-liposomes combined with low intensity focused ultrasound on proliferation of HepG2 cells and its CT imaging in vitro[J]. Journal of Third Military Medical University, 2018, 40(23): 2180-2189. DOI： 10.16016/j.1000-5404.201806153.

摘要

目的

制备一种载血卟啉单甲醚(hematoporphyrin monomethyl ether

HMME)包裹全氟溴辛烷(1-Bromoheptadecafluorooctane

PFOB)及阿霉素(doxorubicin

DOX)的声敏型脂质纳米粒(sound sensitive nano-liposomes

SNLs)

探究其联合低功率聚焦超声(low intensity focused ultrasound

LIFU)体外释药、产生活性氧的能力以及对HepG2细胞增殖的影响

和其体外CT成像的能力。

方法

采用薄膜水化法制备SNL; 检测其一般性质; 高效液相色谱法检测其体外释药; 荧光分光光度计和激光共聚焦显微镜观察其产生活性氧的能力; CCK-8实验检测其对HepG2细胞增殖的影响

CT观察其体外CT成像。

结果

成功制备SNL

粒径为(282.53±6.95)nm; LIFU处理8h内SNL释放阿霉素达(83.45±2.97)%

释药速度随LIFU强度提高而加快; 以DPBF(1

3-二苯基异苯并呋喃)为活性氧探针

产生活性氧的相对量随SNL中血卟啉单甲醚增加及LIFU强度增高而增多; 以DCFH-DA(2′

7′-二氯荧光黄双乙酸盐)为活性氧探针

激光共聚焦观察显示SNL+LIFU组较SNL组绿色荧光强; CCK-8检测结果显示SNL+LIFU组的细胞存活率明显较DOX组

载血卟啉单甲醚包裹全氟溴辛烷的脂质纳米粒(hematoporphyrin monomethyl ether nano-liposomes

HNL)+LIFU组和SNL组低(

0.05)

可见SNL+LIFU明显增强了对HepG2细胞生长的抑制作用; CT成像结果显示SNL的CT值较对照组和空白组高

且CT值随PFOB浓度增大而增高。

结论

成功制备的声敏型脂质纳米粒的声动力效果呈HMME浓度及LIFU强度依赖性

药物释放速度受LIFU控制

可联合化疗及声动力治疗增强HepG2细胞生长的抑制效果

同时具有良好的CT成像效果。

Abstract

Objective

To prepare a sound sensitive nano-liposomes (SNLs) loaded with hematoporphyrin monomethyl ether (HMME)

1-bromoheptadecafluorooctane (PFOB) and doxorubicin (DOX)

and to investigate their abilities in releasing drugs

generating reactive oxygen species (ROS) and inhibiting HepG2 cells proliferation under low intensity focused ultrasound (LIFU) and explore its CT imaging

in vitro

Methods

SNLs were prepared by membrane hydration

and their basic features were tested. After LIFU

the drug-release of SNLs was detected by high performance liquid chromatography (HPLC). The ability of SNLs to produce ROS was detected

via

fluorescence spectrophotometry and observed

via

laser confocal microscopy. The proliferation of HepG2 cells was detected by CCK-8 assay and CT imaging was observed by Philips Ingenuity CT scanner.

Results

SNLs were successfully prepared with their particle size of 282.53±6.95 nm. Under LIFU irradiation within 8 h

the nano-liposomes released (83.45±2.97)% DOX

and the releasing speed was increased with the increase of LIFU intensity. With DPBF as ROS probe

the relative amount of produced ROS was increased

as the dose of HMME or the intensity of LIFU rose. When DCFH-DA was used as ROS probe

the green fluorescence in the HepG2 cells treated with SNLs+LIFU was brighter than those treated with SNLs alone. The results of CCK-8 assay indicated that SNL+LIFU treatment decreased the cell viability than the cells treated with DOX or SNLs alone

and HMME nano-liposomes (HNL)+LIFU (

0.05)

indicating that SNL+LIFU treatment enhancing the inhibition on HepG2 cells proliferation. The CT value in SNL was higher than it in control group or blank group

and the value was increased as the increase of PFOB dose.

Conclusion

The sonodynamic effect of our prepared SNLs is in a HMME-dose and LIFU-intensity dependent manner. LIFU can prompt drug release in the nano-liposomes. SNLs+LIFU combined with sonodynamic therapy and chemotherapy enhances the inhibition on HepG2 cells proliferation. Besides

SNL can be used in CT imaging

in vitro

关键词

Keywords

references

DA MOTTA GIRARDI D, CORREA T S, CROSARA TEIXEIRA M, et al.Hepatocellular carcinoma:review of targeted and immune therapies[J]. J Gastrointest Cancer, 2018, 49(3):227-236.DOI:10.1007/s12029-018-0121-4.

广东省抗癌协会肝癌专业委员会.肝癌多学科联合治疗策略与方法——广东专家共识(2)[J].临床肝胆病杂志, 2014, 30(11):1116-1119.DOI:10.3969/j.issn.1001-5256.2014.11.005.

Society of Liver Cancer, Guangdong Provincial Anti-Cancer Association. Strategy and method of multi-disciplinary team for comprehensive treatment of liver cancer-consensus of experts in Guangdong, China (2)[J]. J Clin Hepatol, 2014, 30(11):1116-1119. DOI:10.3969/j.issn.1001-5256.2014.11.005.

WAN G, LIU Y, SHI S, et al. Hematoporphyrin and doxorubicin co-loaded nanomicelles for the reversal of drug resistancein human breast cancer cells by combining sonodynamic therapyand chemotherapy[J]. RSC Advances, 2016, 6(102):100361-100372. DOI:10.1039/C6RA22724D.

PAN X, WANG H, WANG S, et al. Sonodynamic therapy (SDT): a novel strategy for cancer nanotheranostics[J]. Sci China Life Sci, 2018, 61(4):415-426. DOI: 10.1007/s11427-017-9262-x.

NESBITT H, SHENG Y, KAMILA S, et al. Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of pancreatic cancer[J]. J Control Release, 2018, 279:8-16. DOI: 10.1016/j.jconrel.2018.04.018.

刘韧耕, 李黎波.声动力治疗的研究进展[J].中国激光医学杂志, 2015, 24(3):151-157. DOI:10.13480/j.issn1003-9430.2015.0151.

LIU R G, LI L B. New progress of sonodynamic therapy research[J]. Chin J Laser Med Surg, 2015, 24(3):151-157.DOI:10.13480/j.issn1003-9430.2015.0151.

葛鹏磊, 李宁.高强度聚焦超声治疗肝癌致皮肤烧伤的原因及预防[J].临床超声医学杂志, 2007, 9(10):635-636.DOI:10.16245/j.cnki.issn1008-6978.2007.10.029.

GE P L, LI N.Causes and prevention of skin burns caused by hepatocellular carcinoma treated by high intensity focused ultrasound[J]. J Ultrasound Clin Med, 2007, 9(10):635-636. DOI:10.16245/j.cnki.issn1008-6978.2007.10.029.

OLUSANYA T O B, HAJ AHMAD R R, IBEGBU D M, et al. Liposomal drug delivery systems and anticancer drugs[J]. Molecules, 2018, 23(4):E907.DOI:10.3390/molecules23040907.

黄苏苏, 谢波, 凌家俊, 等.二氢卟吩e6磁性声敏纳米脂质体的制备及质量评价[J].中国实验方剂学杂志, 2017, 23(8):21-26. DOI: 10.13422/j.cnki.syfjx.2017080021.

HUANG S S, XIE B, LING J J, et al.Preparation and qualityevaluation of magnetic sound sensitive nano-liposomes with porphyrin e6[J]. Chin J Exp Tradit Med Formulae, 2017, 23(8):21-26.DOI:10.13422/j.cnki.syfjx.2017080021.

李奥, 王志刚, 余进洪, 等.液态氟碳纳米粒增强CT成像在兔VX2肝癌模型中的应用[J].中国医学影像技术, 2010, 26(5):809-811.DOI:10.13929/j.1003-3289.2010.05.047.

LI A, WANG Z G, YU J H, et al. Lipid perfluorooctylbromidenanoparticles-enhanced CT imaging on rabbit VX2 liver carcinoma models[J]. Chin J Med Imaging Technol, 2010, 26(5):809-811.DOI:10.13929/j.1003-3289.2010.05.047.

SHENG D, LIU T, DENG L, et al. Perfluorooctyl bromide&indocyanine green co-loaded nanoliposomes for enhanced multimodal imaging-guided phototherapy[J]. Biomaterials, 2018, 165:1-13.DOI:10.1016/j.biomaterials.2018.02.041.

周洋.相变纳米超声造影剂增效HIFU治疗作用的研究[D].重庆: 重庆医科大学, 2012.

ZHOU Y.Application of a phase-change type nano-size ultrasound contrast agent to enhance the efficacy of HIFU ablation[D]. Chongqing: Chongqing Medical University, 2012.

YAN F, DUAN W, LI Y, et al. NIR-laser-controlled drug release from DOX/IR-780-loaded temperature-sensitive-liposomes for chemo-photothermal synergistic tumor therapy[J]. Theranostics, 2016, 6(13):2337-2351.DOI:10.7150/thno.14937.

SHI J, SU Y, LIU W, et al. A nanoliposome-based photoactivable drug delivery system for enhanced cancer therapy and overcoming treatment resistance[J]. Int J Nanomedicine, 2017, 12:8257-8275. DOI:10.2147/IJN.S143776.

陈佳丽.白藜芦醇苷对人肝癌细胞HepG2细胞株凋亡的促进作用的实验研究[D].广州: 南方医科大学, 2017.

CHEN J L.The study of effect of Polydatin on apoptosis of human hepatocellular carcinoma cell line[D]. Guangzhou: Southern Medical University, 2017.

唐琴.携氧载吲哚菁绿纳米粒协同光-声动力对类风湿关节炎滑膜成纤维细胞的毒性作用研究[D].重庆: 重庆医科大学, 2017.

TANG Q.Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes[D]. Chongqing: Chongqing Medical University, 2017.

FENG Q, LI Y, YANG X,et al. Hypoxia-specific therapeuticagents delivery nanotheranostics: A sequential strategyfor ultrasound mediated on-demand tritherapies and imaging of cancer[J]. J Controlled Release, 2018, 275: 192-200.DOI:10.1016/j.jconrel.2018.02.011.

REN H, LIU J, SU F, et al. Relighting photosensitizers by synergistic integration of albumin and perfluorocarbon for enhanced photodynamic therapy[J]. ACS Appl Mater Interfaces, 2017, 9(4):3463-3473. DOI: 10.1021/acsami.6b14885.

MILLER D L, AVERKIOU M A, BRAYMAN A A, et al. Bioeffects considerations for diagnostic ultrasound contrast agents[J]. J Ultrasound Med, 2008, 27(4):611-632.DOI:10.7863/jum.2008.27.4.611.

DEEPAGAN V G, YOU D G, UM W, et al. Long-circulating Au-TiO2 nanocomposite as a sonosensitizer for ROS-mediatederadication of cancer[J]. Nano Lett, 2016, 16(10):6257-6264.DOI:10.1021/acs.nanolett.6b02547.

QIAO Y, WAN J, ZHOU L, et al. Stimuli-responsive nanotherapeutics for precision drug delivery and cancer therapy[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2018:e1527.DOI: 10.1002/wnan.1527.

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Effect of sound sensitive nano-liposomes combined with low intensity focused ultrasound on proliferation of HepG2 cells and its CT imaging in vitro

DOI：10.16016/j.1000-5404.201806153

摘要

Abstract

关键词

Keywords

references