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基于乏氧环境的生物靶向载药纳米粒诊疗乳腺癌的实验研究
Efficacy of bio-targeted drug-loaded nanoparticles on diagnosis and treatment for breast cancer based on hypoxic environment
- 第三军医大学学报 2021年43卷第10期 页码：946-954
- 作者机构：
- 作者简介：
- 基金信息：
DOI：10.16016/j.1000-5404.202012046
中图分类号：收稿：2020-12-05，
纸质出版：2021-05-30
- 稿件说明：
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王璐, 蒋富杰, 杨海燕, 等. 基于乏氧环境的生物靶向载药纳米粒诊疗乳腺癌的实验研究[J]. 第三军医大学学报, 2021,43(10):946-954.
Lu WANG, Fujie JIANG, Haiyan YANG, et al. Efficacy of bio-targeted drug-loaded nanoparticles on diagnosis and treatment for breast cancer based on hypoxic environment[J]. Journal of Third Military Medical University, 2021, 43(10): 946-954.
王璐, 蒋富杰, 杨海燕, 等. 基于乏氧环境的生物靶向载药纳米粒诊疗乳腺癌的实验研究[J]. 第三军医大学学报, 2021,43(10):946-954. DOI： 10.16016/j.1000-5404.202012046.
Lu WANG, Fujie JIANG, Haiyan YANG, et al. Efficacy of bio-targeted drug-loaded nanoparticles on diagnosis and treatment for breast cancer based on hypoxic environment[J]. Journal of Third Military Medical University, 2021, 43(10): 946-954. DOI： 10.16016/j.1000-5404.202012046.
摘要
Abstract
Objective
2
To investigate the efficacy of bio-targeted drug loaded nanoparticles for the diagnosis and treatment of breast cancer based on tumor hypoxia microenvironment.
Methods
2
Lipid nanoparticles loaded with perfluorohexane (PFH) and tirazamine (TPZ) were prepared by film hydration. Bifidobacteria were cultured and detected for basic characterizations. Then
the bacteria and nanoparticles were connected by electrostatic adsorption to prepare bio-targeted drug-loaded nanoparticles
and laser confocal microscopy and flow cytometry were used to detect the binding between them. Ultrasonic diagnostic imaging
MTT assay and flow cytometry were adopted to observe the
in vitro
imaging performance and killing effect on breast cancer cells after high-intensity focused ultrasound (HIFU) irradiation. Tissue homogenate was used to observe the targeting ability of bifidobacteria.
In vivo
fluorescence imaging was performed to monitor the targeting of nanoparticles. The 4T1 breast tumor-bearing mice were established and randomly divided into targeted group (
n
=3) and non-targeted group (
n
=3) to observe the ultrasound imaging performance of nanoparticles. The tumor-bearing mice were randomly divided into blank control group
PBS+HIFU group
nonoparticles+HIFU group
and nonoparticles+ bifidobacterium+HIFU group (
n
=3 for each group). The body weight and tumor volume were recorded during treatment process
HE staining was performed 14 d later to observe the morphological changes of the tumor mass.
Results
2
Bio-targeted drug loaded nanoparticles were successfully prepared. The nanoparticles had an average size of 218.93±6.56 nm and a zet
a potential of 55.00±4.97 mV
and the bifidobacterium had a potential of -28.10±7.52 mV. The connection rate of the nanoparticles and bacterium was (99.04±0.40)%. The nanoparticles showed better ultrasound imaging after HIFU irradiation. The results of MTT assay and flow cytometry showed that the nanoparticles exerted better killing effect on breast cancer cells under hypoxic condition than under normoxia condition (
P
<
0.05). The results of tissue homogenate demonstrated that bifidobacteria showed good target ability.
In vivo
fluorescence imaging displayed that the nanoparticles were enriched around the tumor.
In vivo
ultrasound imaging was achieved in the targeted group after HIFU irradiation. Both the records of tumor volume and results of HE staining indicated that the nonoparticles+bifidobacterium+HIFU group got the best tumor inhibitory effect (
P
<
0.05).
Conclusion
2
The bio-targeted drug loaded nanoparticles can effectively diagnose and treat breast cancer based on hypoxia microenvironment. Our study provides a new thought for the integration of tumor diagnosis and treatment.
关键词
Keywords
references
SHANNON A M BOUCHIER-HAYES D J CONDRON C M Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies Cancer Treat Rev 2003 Aug; 29 4 297 307 10.1016/s0305-7372(03)00003-3 SHANNON A M, BOUCHIER-HAYES D J, CONDRON C M, et al . Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies[J ] . Cancer Treat Rev, 2003 Aug; 29(4): 297-307. DOI: 10.1016/s0305-7372(03)00003-3.
XU D ZOUW J LUO Y Feasibility between bifidobacteria targeting and changes in the acoustic environment of tumor tissue for synergistic HIFU Sci Rep 2020 10 1 7772 10.1038/s41598-020-64661-6 XU D, ZOUW J, LUO Y, et al . Feasibility between bifidobacteria targeting and changes in the acoustic environment of tumor tissue for synergistic HIFU[J ] . Sci Rep, 2020, 10(1): 7772. DOI: 10.1038/s41598-020-64661-6.
GAO X ZOU W JIANG B L Experimental study of retention on the combination of bifidobacterium with high-intensity focused ultrasound (HIFU) synergistic substance in tumor tissues Sci Rep 2019 9 1 6423 10.1038/s41598-019-42832-4 GAO X, ZOU W, JIANG B L, et al . Experimental study of retention on the combination of bifidobacterium with high-intensity focused ultrasound (HIFU) synergistic substance in tumor tissues [J ] . Sci Rep, 2019, 9(1): 6423. DOI: 10.1038/s41598-019-42832-4.
LUO Y XU D GAO X Nanoparticles conjugated with bacteria targeting tumors for precision imaging and therapy Biochem Biophys Res Commun 2019 514 4 1147 1153 10.1016/j.bbrc.2019.05.074 LUO Y, XU D, GAO X, et al . Nanoparticles conjugated with bacteria targeting tumors for precision imaging and therapy[J ] . Biochem Biophys Res Commun, 2019, 514(4): 1147-1153. DOI: 10.1016/j.bbrc.2019.05.074.
WANG Y T CHEN C LUO Y Experimental study of tumor therapy mediated by multimodal imaging based on a biological targeting synergistic agent Int J Nanomed 2020 15 1871-88 10.2147/IJN.S238398 WANG Y T, CHEN C, LUO Y, et al . Experimental study of tumor therapy mediated by multimodal imaging based on a biological targeting synergistic agent [J ] . Int J Nanomed, 2020, 15(1871-88). DOI: 10.2147/IJN.S238398.
CHEN C WANGY TANG Y Bifidobacterium-mediated high-intensity focused ultrasound for solid tumor therapy: comparison of two nanoparticle delivery methods Int J Hyperthermia 2020 37 1 870 878 10.1080/02656736.2020.1791365 CHEN C, WANGY, TANG Y, et al . Bifidobacterium-mediated high-intensity focused ultrasound for solid tumor therapy: comparison of two nanoparticle delivery methods[J ] . Int J Hyperthermia, 2020, 37(1): 870-878. DOI: 10.1080/02656736.2020.1791365.
PHILLIPSR M Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs Cancer Chemother Pharmacol 2016 77 3 441 457 10.1007/s00280-015-2920-7 PHILLIPSR M. Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs[J]. Cancer Chemother Pharmacol, 2016, 77(3): 441-457. DOI: 10.1007/s00280-015-2920-7.
HONGB J KIM J JEONG H Tumor hypoxia and reoxygenation: the Yin and Yang for radiotherapy Radiat Oncol J 2016 34 4 239 249 10.3857/roj.2016.02012 HONGB J, KIM J, JEONG H, et al . Tumor hypoxia and reoxygenation: the Yin and Yang for radiotherapy[J ] . Radiat Oncol J, 2016, 34(4): 239-249. DOI: 10.3857/roj.2016.02012.
OERLEMANS C DECKERS R STORM G Evidence for a new mechanism behind HIFU-triggered release from liposomes J Control Release 2013 168 3 327 333 10.1016/j.jconrel.2013.03.019 OERLEMANS C, DECKERS R, STORM G, et al . Evidence for a new mechanism behind HIFU-triggered release from liposomes[J ] . J Control Release, 2013, 168(3): 327-333. DOI: 10.1016/j.jconrel.2013.03.019.
XIA H ZHAO Y TONG R Ultrasound-mediated polymeric micelle drug delivery Adv Exp Med Biol 2016 880 365 384 10.1007/978-3-319-22536-4_20 XIA H, ZHAO Y, TONG R. Ultrasound-mediated polymeric micelle drug delivery[J]. Adv Exp Med Biol, 2016, 880: 365-384. DOI: 10.1007/978-3-319-22536-4_20.
ARORA J S MURAD H Y ASHE S Ablative focused ultrasound synergistically enhances thermally triggered chemotherapy for prostate cancer in vitro Mol Pharm 2016 Sep 6;13 9 3080 3090 10.1021/acs.molpharmaceut.6b00216 ARORA J S, MURAD H Y, ASHE S, et al . Ablative focused ultrasound synergistically enhances thermally triggered chemotherapy for prostate cancer in vitro [J ] . Mol Pharm, 2016 Sep 6;13(9): 3080-3090. DOI: 10.1021/acs.molpharmaceut.6b00216.
ZHANG N CAI X GAO W A multifunctional theranostic nanoagent for dual-mode image-guided HIFU/chemo-synergistic cancer therapy Theranostics 2016 6 3 404 417 10.7150/thno.13478 ZHANG N, CAI X, GAO W, et al . A multifunctional theranostic nanoagent for dual-mode image-guided HIFU/chemo-synergistic cance r therapy[J ] . Theranostics, 2016, 6(3): 404-417. DOI: 10.7150/thno.13478.
TANGH GUO Y PENG L In vivo targeted, responsive, and synergistic cancer nanotheranostics by magnetic resonance imaging-guided synergistic high-intensity focused ultrasound ablation and chemotherapy ACS Appl Mater Interfaces 2018 10 18 15428 15441 10.1021/acsami.8b01967 TANGH, GUO Y, PENG L, et al . In vivo targeted, responsive, and synergistic cancer nanotheranostics by magnetic resonance imaging-guided synergistic high-intensity focused ultrasound ablation and chemotherapy[J ] . ACS Appl Mater Interfaces, 2018, 10(18): 15428-15441. DOI: 10.1021/acsami.8b01967.
ZOU M LIY H XIA S Knockdown of CAVEOLIN-1 sensitizes human basal-like triple-negative breast cancer cells to radiation Cell Physiol Biochem 2017 44 2 778 791 10.1159/000485291 ZOU M, LIY H, XIA S, et al . Knockdown of CAVEOLIN-1 sensitizes human basal-like triple-negative breast cancer cells to radiation[J ] . Cell Physiol Biochem, 2017, 44(2): 778-791. DOI: 10.1159/000485291.
GIORDANO L GALLO F PETRACCI E The ANDROMEDA prospective cohort study: predictive relue of combined criteria to tailor beast cancer screening and new opportunitres from crrculatng markers: Study protocol BMC Cancer 2017 22,17 1 785 10.1186/S12885-017-3784-5 GIORDANO L, GALLO F, PETRACCI E, et al . The ANDROMEDA prospective cohort study: predictive relue of combined criteria to tailor beast cancer screening and new opportunitres from crrculatng markers: Study protocol[J ] . BMC Cancer, 2017, 22, 17(1): 785. DOI: 10.1186/S12885-017-3784-5.
BAHRAMI B HOJJAT-FARSANGI M MOHAMMADI H Nanoparticles and targeted drug delivery in cancer therapy Immunol Lett 2017 190 64 83 10.1016/j.imlet.2017.07.015 BAHRAMI B, HOJJAT-FARSANGI M, MOHAMMADI H, et al . Nanoparticles and targeted dr ug delivery in cancer therapy[J ] . Immunol Lett, 2017, 190: 64-83. DOI: 10.1016/j.imlet.2017.07.015.
ST JEAN A T ZHANG M FORBES N S Bacterial therapies: completing the cancer treatment toolbox Curr Opin Biotechnol 2008 19 5 511 517 10.1016/j.copbio.2008.08.004 ST JEAN A T, ZHANG M, FORBES N S. Bacterial therapies: completing the cancer treatment toolbox[J]. Curr Opin Biotechnol, 2008, 19(5): 511-517. DOI: 10.1016/j.copbio.2008.08.004.
DUONGM T QIN Y YOU S H Bacteria-cancer interactions: bacteria-based cancer therapy Exp Mol Med 2019 51 12 1 15 10.1038/s12276-019-0297-0 DUONGM T, QIN Y, YOU S H, et al . Bacteria-cancer interactions: bacteria-based cancer therapy[J ] . Exp Mol Med, 2019, 51(12): 1-15. DOI: 10.1038/s12276-019-0297-0.
YANG S TANG Z HU C Selectively potentiating hypoxia levels by combretastatin A4 nanomedicine: toward highly enhanced hypoxia-activated prodrug tirapazamine therapy for metastatic tumors Adv Mater 2019 31 11 e1805955 10.1002/adma.201805955 YANG S, TANG Z, HU C, et al . Selectively potentiating hypoxia levels by combretastatin A4 nanomedicine: toward highly enhanced hypoxia-activated prodrug tirapazamine therapy for metastatic tumors[J ] . Adv Mater, 2019, 31(11): e1805955. DOI: 10.1002/adma.201805955.
WANG Y XIE Y LI J Tumor-penetrating nanoparticles for enhanced anticancer activity of combined photodynamic and hypoxia-activated therapy ACS Nano 2017 11 2 2227 2238 10.1021/acsnano.6b08731 WANG Y, XIE Y, LI J, et al . Tumor-penetrating nanoparticles for enhanced anticancer activity of combined photodynamic and hypoxia-activated therapy[J ] . ACS Nano, 2017, 11(2): 2227-2238. DOI: 10.1021/acsnano.6b08731.
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