Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer
Identifieur interne : 000147 ( Pmc/Checkpoint ); précédent : 000146; suivant : 000148Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer
Auteurs : Lu Yang [République populaire de Chine] ; Juan Cheng [République populaire de Chine] ; Yuli Chen [République populaire de Chine] ; Shengjie Yu [République populaire de Chine] ; Fengqiu Liu [République populaire de Chine] ; Yang Sun [République populaire de Chine] ; Yu Chen [République populaire de Chine] ; Haitao Ran [République populaire de Chine]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
Pathological status of lymph nodes (LNs) plays a critical role in staging and treatment for the patients with breast cancer. Sentinel lymph node biopsy has become the standard method in determining pathological status of axillary LNs. Therefore, the determination of sentinel lymph nodes (SLNs) and therapy of metastatic LNs are highly desirable in clinic. Herein, an unprecedented carbon nanoparticles (CNs)-incorporated liquid-gas phase-transition nanodroplets (CNPs) with strong near-infrared (NIR) absorption, good biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, and high photothermal-conversion efficiency are reported in this study. Upon laser irradiation, liquid-gas phase transition of the CNPs has been demonstrated to provide excellent contrasts for PA/US dual-modality imaging both
Url:
DOI: 10.1038/srep45213
PubMed: 28338071
PubMed Central: 5364557
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer</title><author><name sortKey="Yang, Lu" sort="Yang, Lu" uniqKey="Yang L" first="Lu" last="Yang">Lu Yang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Breast, Thyriod, Pancreas Surgery, Second Affiliated Hospital of Chongqing Medical University</institution>, Chongqing 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Juan" sort="Cheng, Juan" uniqKey="Cheng J" first="Juan" last="Cheng">Juan Cheng</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yuli" sort="Chen, Yuli" uniqKey="Chen Y" first="Yuli" last="Chen">Yuli Chen</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yu, Shengjie" sort="Yu, Shengjie" uniqKey="Yu S" first="Shengjie" last="Yu">Shengjie Yu</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Urinary Surgery, Second Affiliated Hospital of Chongqing Medical University</institution>, Chongqing 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Fengqiu" sort="Liu, Fengqiu" uniqKey="Liu F" first="Fengqiu" last="Liu">Fengqiu Liu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Yang" sort="Sun, Yang" uniqKey="Sun Y" first="Yang" last="Sun">Yang Sun</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences</institution>, Shanghai, 200050,<country>P. R. China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ran, Haitao" sort="Ran, Haitao" uniqKey="Ran H" first="Haitao" last="Ran">Haitao Ran</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28338071</idno><idno type="pmc">5364557</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364557</idno><idno type="RBID">PMC:5364557</idno><idno type="doi">10.1038/srep45213</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000982</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000982</idno><idno type="wicri:Area/Pmc/Curation">000982</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000982</idno><idno type="wicri:Area/Pmc/Checkpoint">000147</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000147</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer</title><author><name sortKey="Yang, Lu" sort="Yang, Lu" uniqKey="Yang L" first="Lu" last="Yang">Lu Yang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Breast, Thyriod, Pancreas Surgery, Second Affiliated Hospital of Chongqing Medical University</institution>, Chongqing 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Juan" sort="Cheng, Juan" uniqKey="Cheng J" first="Juan" last="Cheng">Juan Cheng</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yuli" sort="Chen, Yuli" uniqKey="Chen Y" first="Yuli" last="Chen">Yuli Chen</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yu, Shengjie" sort="Yu, Shengjie" uniqKey="Yu S" first="Shengjie" last="Yu">Shengjie Yu</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Urinary Surgery, Second Affiliated Hospital of Chongqing Medical University</institution>, Chongqing 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Fengqiu" sort="Liu, Fengqiu" uniqKey="Liu F" first="Fengqiu" last="Liu">Fengqiu Liu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Yang" sort="Sun, Yang" uniqKey="Sun Y" first="Yang" last="Sun">Yang Sun</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences</institution>, Shanghai, 200050,<country>P. R. China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ran, Haitao" sort="Ran, Haitao" uniqKey="Ran H" first="Haitao" last="Ran">Haitao Ran</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Pathological status of lymph nodes (LNs) plays a critical role in staging and treatment for the patients with breast cancer. Sentinel lymph node biopsy has become the standard method in determining pathological status of axillary LNs. Therefore, the determination of sentinel lymph nodes (SLNs) and therapy of metastatic LNs are highly desirable in clinic. Herein, an unprecedented carbon nanoparticles (CNs)-incorporated liquid-gas phase-transition nanodroplets (CNPs) with strong near-infrared (NIR) absorption, good biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, and high photothermal-conversion efficiency are reported in this study. Upon laser irradiation, liquid-gas phase transition of the CNPs has been demonstrated to provide excellent contrasts for PA/US dual-modality imaging both <italic>in vitro</italic> and <italic>in vivo</italic>. Additionally, the CNPs are capable of staining lymph nodes, which can contribute significantly to the identification of LNs with naked eyes. With increased laser energy, the CNPs exhibit the high performance in killing the breast cancer cells both <italic>in vitro</italic> and <italic>in vivo</italic>, due to the photothermal effect induced from the CNs within CNPs. These results suggest that the developed multifunctional phase-transition nanodroplets have high potential to act as the theranostic agents in both SLNs detection and therapy of metastatic LNs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lin, W" uniqKey="Lin W">W. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liang, X" uniqKey="Liang X">X. Liang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, S" uniqKey="Zhang S">S. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jian, J" uniqKey="Jian J">J. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28338071</article-id><article-id pub-id-type="pmc">5364557</article-id><article-id pub-id-type="pii">srep45213</article-id><article-id pub-id-type="doi">10.1038/srep45213</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Lu</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref><xref ref-type="author-notes" rid="n1">*</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Juan</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="author-notes" rid="n1">*</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Yuli</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Shengjie</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Fengqiu</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Yang</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Yu</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ran</surname><given-names>Haitao</given-names></name><xref ref-type="corresp" rid="c2">b</xref><xref ref-type="aff" rid="a1">1</xref></contrib><aff id="a1"><label>1</label><institution>Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging</institution>, Chongqing, 400010,<country>China</country></aff><aff id="a2"><label>2</label><institution>Department of Breast, Thyriod, Pancreas Surgery, Second Affiliated Hospital of Chongqing Medical University</institution>, Chongqing 400010,<country>China</country></aff><aff id="a3"><label>3</label><institution>Department of Urinary Surgery, Second Affiliated Hospital of Chongqing Medical University</institution>, Chongqing 400010,<country>China</country></aff><aff id="a4"><label>4</label><institution>State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences</institution>, Shanghai, 200050,<country>P. R. China</country></aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>chenyu@mail.sic.ac.cn</email></corresp><corresp id="c2"><label>b</label><email>300190@hospital.cqmu.edu.cn</email></corresp><fn id="n1"><label>*</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>24</day><month>03</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>7</volume><elocation-id>45213</elocation-id><history><date date-type="received"><day>24</day><month>11</month><year>2016</year></date><date date-type="accepted"><day>21</day><month>02</month><year>2017</year></date></history><permissions><copyright-statement>Copyright © 2017, The Author(s)</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>The Author(s)</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>Pathological status of lymph nodes (LNs) plays a critical role in staging and treatment for the patients with breast cancer. Sentinel lymph node biopsy has become the standard method in determining pathological status of axillary LNs. Therefore, the determination of sentinel lymph nodes (SLNs) and therapy of metastatic LNs are highly desirable in clinic. Herein, an unprecedented carbon nanoparticles (CNs)-incorporated liquid-gas phase-transition nanodroplets (CNPs) with strong near-infrared (NIR) absorption, good biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, and high photothermal-conversion efficiency are reported in this study. Upon laser irradiation, liquid-gas phase transition of the CNPs has been demonstrated to provide excellent contrasts for PA/US dual-modality imaging both <italic>in vitro</italic> and <italic>in vivo</italic>. Additionally, the CNPs are capable of staining lymph nodes, which can contribute significantly to the identification of LNs with naked eyes. With increased laser energy, the CNPs exhibit the high performance in killing the breast cancer cells both <italic>in vitro</italic> and <italic>in vivo</italic>, due to the photothermal effect induced from the CNs within CNPs. These results suggest that the developed multifunctional phase-transition nanodroplets have high potential to act as the theranostic agents in both SLNs detection and therapy of metastatic LNs.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><p>(<bold>A)</bold>, schematic diagram of the fabrication process for carbon nanoparticles nanodroplets (CNPs) (a–e). (<bold>B</bold>). perfluorohexane (PFH) liquid-gas transition after laser irradiation (a–c).</p></caption><graphic xlink:href="srep45213-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><p>(<bold>A)</bold> (a and b), optical microscopic images of the CNPs before and after laser irradiation. The white arrows in (b) indicate the phase transition of CNPs. (<bold>B)</bold>, (a), transmission electron microscope (TEM) images of a CNP. Black granular carbon nanoparticles (CNs) and gray black PFH were encapsulated in the white poly(lactide-co-glycolide acid) (PLGA) shell; (b), TEM images of CNs. (<bold>C</bold>), the optical density of CNPs, pure CNs and NPs, as measured by spectrophotometry. (<bold>D</bold>), cytotoxicity results of CNPs on RAW264.7 cells (mean ± standard deviation for different concentrations of CNPs).</p></caption><graphic xlink:href="srep45213-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><p>(<bold>A)</bold>, (a), fluorescence microscope image of Dil-labeled CNPs. (b and c), optical microscope and fluorescence microscope image of CNPs phagocytosed by macrophages, respectively. (<bold>B)</bold>, (a), hematoxylin-eosin (HE) staining of metastatic LN tissues after CNPs injection for 48 h. The black arrows indicate the macrophages phagocytized CNPs. (b), HE staining of metastatic LN tissues after CNPs injection for 48 h. The black arrows indicate the CNPs were around the tumor cells.</p></caption><graphic xlink:href="srep45213-f3"></graphic></fig><fig id="f4"><label>Figure 4</label><caption><p>(<bold>A</bold>), photoacoustic (PA) images of 5, 10, 15 and 20 mg/mL CNPs in 0.2% agarose gel after irradiation. (<bold>B</bold>), the quantitative analysis of the PA signal intensity of concentrations in (<bold>A</bold>). (<bold>C</bold>), contrast-enhanced ultrasonography (CEUS) images of 5, 10, 15 and 20 mg/mL CNPs in 0.2% agarose gel after irradiation (808 nm, 1 W/cm<sup>2</sup>) for 10 s. (<bold>D</bold>), quantitative analysis of the average gray scale in concentrations in (<bold>C)</bold>.</p></caption><graphic xlink:href="srep45213-f4"></graphic></fig><fig id="f5"><label>Figure 5</label><caption><p>(<bold>A</bold>), a1, B-mode image of lymph node (LN); a2, PA-mode image of LN before CNPs injection, a3-a6, PA-mode images of LNs after CNPs injection at different time points (15 min, 1 h, 24 h, 48 h). (<bold>B</bold>), quantitative analysis of the PA signal intensity in <bold>A</bold>. (<bold>C</bold>). a1, b1, c1, B-mode image of LNs before agents (NPs, CNPs and CNs) injection, a2, b2, c2, PA-mode image of LNs after agents injection at 15 min, a3, b3, c3, PA-mode image of LNs after agents injection at 1 h, a4, b4, c4, PA-mode image of LNs after agents injection at 24 h. (<bold>D</bold>). quantitative analysis of the PA signals intensity in <bold>C</bold> (*p < 0.05).</p></caption><graphic xlink:href="srep45213-f5"></graphic></fig><fig id="f6"><label>Figure 6</label><caption><p>(<bold>A</bold>), a1, B-mode image of LNs; a2, contrast-mode image of LN before CNPs injection, a3-a6, contrast-mode images of LNs after CNPs injection (15 min, 1 h, 2 h, 24 h). (<bold>B</bold>), quantitative analysis of the PA signal intensity in <bold>A. (C</bold>). a1, b1, c1, B-mode images of LNs; a2-a4, b2-b4, c2-c4, PA-mode images of LNs after NPs, CNPs and CNs injection at different time points (15 min, 1 h and 24 h). (<bold>D</bold>), quantitative analysis of the PA signal intensity in <bold>C</bold> (*p < 0.05).</p></caption><graphic xlink:href="srep45213-f6"></graphic></fig><fig id="f7"><label>Figure 7</label><caption><p>(<bold>a</bold>), the popliteal fossa lymph node in rabbit as stained black. (<bold>b</bold>), the removed dyed LN. (<bold>c)</bold>, the LN injected with saline, exhibiting no signs of staining.</p></caption><graphic xlink:href="srep45213-f7"></graphic></fig><fig id="f8"><label>Figure 8</label><caption><p>(<bold>A)</bold>, HE staining of metastatic LN tissues after laser exposure. a1–3, injection with NPs after irradiation for 2, 4, 8 min. b1–3, injection with CNs after irradiation for 2, 4, 8 min. c1–3, injection with CNPs after irradiation for 2, 4, 8 min. (<bold>B</bold>), the apoptosis index of different groups after laser exposure for 30, 60 and 120 s (*p < 0.05).</p></caption><graphic xlink:href="srep45213-f8"></graphic></fig></floats-group></pmc><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Yang, Lu" sort="Yang, Lu" uniqKey="Yang L" first="Lu" last="Yang">Lu Yang</name></noRegion><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><name sortKey="Chen, Yuli" sort="Chen, Yuli" uniqKey="Chen Y" first="Yuli" last="Chen">Yuli Chen</name><name sortKey="Cheng, Juan" sort="Cheng, Juan" uniqKey="Cheng J" first="Juan" last="Cheng">Juan Cheng</name><name sortKey="Liu, Fengqiu" sort="Liu, Fengqiu" uniqKey="Liu F" first="Fengqiu" last="Liu">Fengqiu Liu</name><name sortKey="Ran, Haitao" sort="Ran, Haitao" uniqKey="Ran H" first="Haitao" last="Ran">Haitao Ran</name><name sortKey="Sun, Yang" sort="Sun, Yang" uniqKey="Sun Y" first="Yang" last="Sun">Yang Sun</name><name sortKey="Yang, Lu" sort="Yang, Lu" uniqKey="Yang L" first="Lu" last="Yang">Lu Yang</name><name sortKey="Yu, Shengjie" sort="Yu, Shengjie" uniqKey="Yu S" first="Shengjie" last="Yu">Shengjie Yu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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