Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs
Identifieur interne : 002363 ( Pmc/Checkpoint ); précédent : 002362; suivant : 002364Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs
Auteurs : Baharak Bahmani [États-Unis] ; Christian Y. Lytle [États-Unis] ; Ameae M. Walker [États-Unis] ; Sharad Gupta [États-Unis] ; Valentine I. Vullev [États-Unis] ; Bahman Anvari [États-Unis]Source :
- International Journal of Nanomedicine [ 1176-9114 ] ; 2013.
Abstract
Near-infrared nanoconstructs present a potentially effective platform for site-specific and deep tissue optical imaging and phototherapy. We have engineered a polymeric nanocapsule composed of polyallylamine hydrochloride (PAH) chains cross-linked with sodium phosphate and doped with indocyanine green (ICG) toward such endeavors. The ICG-doped nanocapsules were coated covalently with polyethylene glycol (5000 daltons) through reductive amination. We administrated the constructs by tail vein injection to healthy mice. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, due to encapsulation, offers the potential of extending the clinical applications of ICG, which are currently limited due to rapid elimination of ICG from the vasculature. Our results also indicate that PAH and ICG-doped nanocapsules (ICG-NCs) are not cytotoxic at the levels used in this study.
Url:
DOI: 10.2147/IJN.S42511
PubMed: 23637530
PubMed Central: 3635661
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Lytle</name><affiliation wicri:level="1"><nlm:aff id="af2-ijn-8-1609">Division of Biomedical Sciences, University of California, Riverside, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biomedical Sciences, University of California, Riverside, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Walker, Ameae M" sort="Walker, Ameae M" uniqKey="Walker A" first="Ameae M" last="Walker">Ameae M. 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Lytle</name><affiliation wicri:level="1"><nlm:aff id="af2-ijn-8-1609">Division of Biomedical Sciences, University of California, Riverside, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biomedical Sciences, University of California, Riverside, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Walker, Ameae M" sort="Walker, Ameae M" uniqKey="Walker A" first="Ameae M" last="Walker">Ameae M. Walker</name><affiliation wicri:level="1"><nlm:aff id="af2-ijn-8-1609">Division of Biomedical Sciences, University of California, Riverside, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biomedical Sciences, University of California, Riverside, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Gupta, Sharad" sort="Gupta, Sharad" uniqKey="Gupta S" first="Sharad" last="Gupta">Sharad Gupta</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-8-1609">Department of Bioengineering, University of California, Riverside, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, University of California, Riverside, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Vullev, Valentine I" sort="Vullev, Valentine I" uniqKey="Vullev V" first="Valentine I" last="Vullev">Valentine I. Vullev</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-8-1609">Department of Bioengineering, University of California, Riverside, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, University of California, Riverside, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Anvari, Bahman" sort="Anvari, Bahman" uniqKey="Anvari B" first="Bahman" last="Anvari">Bahman Anvari</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-8-1609">Department of Bioengineering, University of California, Riverside, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, University of California, Riverside, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author></analytic><series><title level="j">International Journal of Nanomedicine</title><idno type="ISSN">1176-9114</idno><idno type="eISSN">1178-2013</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Near-infrared nanoconstructs present a potentially effective platform for site-specific and deep tissue optical imaging and phototherapy. We have engineered a polymeric nanocapsule composed of polyallylamine hydrochloride (PAH) chains cross-linked with sodium phosphate and doped with indocyanine green (ICG) toward such endeavors. The ICG-doped nanocapsules were coated covalently with polyethylene glycol (5000 daltons) through reductive amination. We administrated the constructs by tail vein injection to healthy mice. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, due to encapsulation, offers the potential of extending the clinical applications of ICG, which are currently limited due to rapid elimination of ICG from the vasculature. Our results also indicate that PAH and ICG-doped nanocapsules (ICG-NCs) are not cytotoxic at the levels used in this study.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Frangioni, J" uniqKey="Frangioni J">J Frangioni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peer, D" uniqKey="Peer D">D Peer</name></author><author><name sortKey="Karp, Jm" uniqKey="Karp J">JM Karp</name></author><author><name sortKey="Hong, S" uniqKey="Hong S">S Hong</name></author><author><name sortKey="Farokhzad, Oc" uniqKey="Farokhzad O">OC Farokhzad</name></author><author><name sortKey="Margalit, R" uniqKey="Margalit R">R Margalit</name></author><author><name sortKey="Langer, R" uniqKey="Langer R">R Langer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sevick Muraca, Em" uniqKey="Sevick Muraca E">EM Sevick-Muraca</name></author><author><name sortKey="Houston, Jp" uniqKey="Houston 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Nanomedicine</journal-id><journal-id journal-id-type="iso-abbrev">Int J Nanomedicine</journal-id><journal-title-group><journal-title>International Journal of Nanomedicine</journal-title></journal-title-group><issn pub-type="ppub">1176-9114</issn><issn pub-type="epub">1178-2013</issn><publisher><publisher-name>Dove Medical Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23637530</article-id><article-id pub-id-type="pmc">3635661</article-id><article-id pub-id-type="doi">10.2147/IJN.S42511</article-id><article-id pub-id-type="publisher-id">ijn-8-1609</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject></subj-group></article-categories><title-group><article-title>Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bahmani</surname><given-names>Baharak</given-names></name><xref ref-type="aff" rid="af1-ijn-8-1609">1</xref><xref ref-type="corresp" rid="c1-ijn-8-1609"></xref></contrib><contrib contrib-type="author"><name><surname>Lytle</surname><given-names>Christian Y</given-names></name><xref ref-type="aff" rid="af2-ijn-8-1609">2</xref></contrib><contrib contrib-type="author"><name><surname>Walker</surname><given-names>Ameae M</given-names></name><xref ref-type="aff" rid="af2-ijn-8-1609">2</xref></contrib><contrib contrib-type="author"><name><surname>Gupta</surname><given-names>Sharad</given-names></name><xref ref-type="aff" rid="af1-ijn-8-1609">1</xref></contrib><contrib contrib-type="author"><name><surname>Vullev</surname><given-names>Valentine I</given-names></name><xref ref-type="aff" rid="af1-ijn-8-1609">1</xref></contrib><contrib contrib-type="author"><name><surname>Anvari</surname><given-names>Bahman</given-names></name><xref ref-type="aff" rid="af1-ijn-8-1609">1</xref></contrib></contrib-group><aff id="af1-ijn-8-1609"><label>1</label>Department of Bioengineering, University of California, Riverside, CA, USA</aff><aff id="af2-ijn-8-1609"><label>2</label>Division of Biomedical Sciences, University of California, Riverside, CA, USA</aff><author-notes><corresp id="c1-ijn-8-1609">Correspondence: Bahman Anvari, University of California, Riverside, Department of Bioengineering, Riverside, California 92521, USA, Tel +1 951 827 5726, Fax +1 951 827 6416, Email <email>anvarib@ucr.edu</email></corresp></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pmc-comment>Dove Press titles changed from ppub to collections in 2009.
Fake ppub written to satisfy Coll Date Type=ppub</pmc-comment>
<pub-date pub-type="ppub"><year>2013</year></pub-date><pub-date pub-type="epub"><day>22</day><month>4</month><year>2013</year></pub-date><volume>8</volume><fpage>1609</fpage><lpage>1620</lpage><permissions><copyright-statement>© 2013 Bahmani et al, publisher and licensee Dove Medical Press Ltd</copyright-statement><copyright-year>2013</copyright-year><license><license-p>This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Near-infrared nanoconstructs present a potentially effective platform for site-specific and deep tissue optical imaging and phototherapy. We have engineered a polymeric nanocapsule composed of polyallylamine hydrochloride (PAH) chains cross-linked with sodium phosphate and doped with indocyanine green (ICG) toward such endeavors. The ICG-doped nanocapsules were coated covalently with polyethylene glycol (5000 daltons) through reductive amination. We administrated the constructs by tail vein injection to healthy mice. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, due to encapsulation, offers the potential of extending the clinical applications of ICG, which are currently limited due to rapid elimination of ICG from the vasculature. Our results also indicate that PAH and ICG-doped nanocapsules (ICG-NCs) are not cytotoxic at the levels used in this study.</p></abstract><kwd-group><title>Keywords</title><kwd>cancer</kwd><kwd>fluorescent imaging</kwd><kwd>nanoprobes</kwd><kwd>near infrared</kwd><kwd>pharmacokinetics</kwd><kwd>phototherapy</kwd><kwd>vascular imaging</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-ijn-8-1609" position="float"><label>Figure 1</label><caption><p>(<bold>A</bold>) Scanning electron microscope image of uncoated indocyanine green-doped nanocapsules (ICG-NCs), and (<bold>B</bold>) Gaussian fits to the diameter distribution profiles of uncoated and polyethylene glycol (PEG)-ylated ICG-NCs in water at 4°C as measured by dynamic light scattering.</p></caption><graphic xlink:href="ijn-8-1609Fig1"></graphic></fig><fig id="f2-ijn-8-1609" position="float"><label>Figure 2</label><caption><p>(<bold>A</bold>) Absorbance and (<bold>B</bold>) fluorescence spectra of indocyanine green (ICG) (9 μM), uncoated and polyethylene glycol (PEG)-coated indocyanine green-doped nanocapsules (ICG-NCs) (λ<sub>ex</sub> = 680 nm).</p></caption><graphic xlink:href="ijn-8-1609Fig2"></graphic></fig><fig id="f3-ijn-8-1609" position="float"><label>Figure 3</label><caption><p>Viability of human dermal vascular endothelial cells after 24 hours’ incubation in media containing one of the following additives: uncoated indocyanine green-doped nanocapsules (ICG-NCs; 4.6 μg/mL), indocyanine green-doped polyethylene glycol-coated nanocapsules (PEG ICG-NCs, 4.5 μg/mL), and polyallylamine hydrochloride (PAH) at two different concentrations.</p><p><bold>Notes:</bold> Cells incubated in media with no additive constituted the negative control, while cells incubated in media with phenol constituted the positive control. Each bar represents the average of three experiments. Error bars represent one standard deviation. Using statistics to analyze the results for ICG-NCs and PAH (6 μg/mL) yielded <italic>P</italic> values > 0.1 when compared with the negative control and <italic>P</italic> values < 10<sup>−4</sup> when compared with the positive control. Therefore, these three tests indicated lack of adverse effects on cell viability. The same analysis for PAH at 12 μg/mL (2.6 times greater than the concentration administered in in vivo studies) yielded <italic>P</italic> values < 10<sup>−3</sup> when compared with the negative control and <italic>P</italic> values < 10<sup>−4</sup> when compared with the positive control.</p></caption><graphic xlink:href="ijn-8-1609Fig3"></graphic></fig><fig id="f4-ijn-8-1609" position="float"><label>Figure 4</label><caption><p>Whole-body fluorescent images of three different mice injected with freely dissolved indocyanine green (ICG) in phosphate-buffered saline (<bold>A</bold>–<bold>E</bold>), uncoated indocyanine green-doped nanocapsules (ICG-NCs) (<bold>F</bold>–<bold>J</bold>), and polyethylene glycol (PEG)-coated ICG-NCs (<bold>K</bold>–<bold>O</bold>) at various times post-injection.</p></caption><graphic xlink:href="ijn-8-1609Fig4"></graphic></fig><fig id="f5-ijn-8-1609" position="float"><label>Figure 5</label><caption><p>Computed image contrast of the abdominal area of mice injected with freely dissolved indocyanine green (ICG) in phosphate-buffered saline, uncoated indocyanine green-doped nanocapsules (ICG-NCs) and polyethylene glycol (PEG)-coated ICG-NCs at various times post-injection.</p><p><bold>Notes:</bold> The exponential fit to each dataset is presented in green (free ICG, R<sup>2</sup> = 0.95), dark grey (uncoated ICG-NCs, R<sup>2</sup> = 0.96) and red (PEG-coated ICG-NCs, R<sup>2</sup> = 0.99). Error bars represent the standard deviation. Asterisks denote statistically significant differences (<italic>P</italic> < 0.05) between the PEG-coated ICG-NCs, uncoated ICG-NCs, and free ICG contrast.</p></caption><graphic xlink:href="ijn-8-1609Fig5"></graphic></fig><fig id="f6-ijn-8-1609" position="float"><label>Figure 6</label><caption><p>Fluorescent images of harvested organs of six mice at 30 and 60 minutes post tail vein administration of free indocyanine green (ICG) (<bold>A</bold> and <bold>B</bold>), uncoated indocyanine green-doped nanocapsules (ICG-NCs) (<bold>C</bold> and <bold>D</bold>) and polyethylene glycol (PEG)-coated ICG-NCs (<bold>E</bold> and <bold>F</bold>).</p></caption><graphic xlink:href="ijn-8-1609Fig6"></graphic></fig><fig id="f7-ijn-8-1609" position="float"><label>Figure 7</label><caption><p>Estimated percentage of indocyanine green (ICG) recovered from blood, heart, kidneys, lungs, spleen, intestine, and liver of the mice injected with freely dissolved ICG in phosphate-buffered saline, uncoated indocyanine green-doped nanocapsules (ICG-NCs), and polyethylene glycol (PEG)-coated ICG-NCs at (<bold>A</bold>) 15, (<bold>B</bold>) 30, and (<bold>C</bold>) 60 minutes post-injection.</p><p><bold>Notes:</bold> Each experiment was repeated five times. Error bars represent standard deviation. Single asterisks denote statistically significant differences of <italic>P</italic> < 0.05 between the shown pairs.</p></caption><graphic xlink:href="ijn-8-1609Fig7"></graphic></fig></floats-group></pmc><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Bahmani, Baharak" sort="Bahmani, Baharak" uniqKey="Bahmani B" first="Baharak" last="Bahmani">Baharak Bahmani</name></noRegion><name sortKey="Anvari, Bahman" sort="Anvari, Bahman" uniqKey="Anvari B" first="Bahman" last="Anvari">Bahman Anvari</name><name sortKey="Gupta, Sharad" sort="Gupta, Sharad" uniqKey="Gupta S" first="Sharad" last="Gupta">Sharad Gupta</name><name sortKey="Lytle, Christian Y" sort="Lytle, Christian Y" uniqKey="Lytle C" first="Christian Y" last="Lytle">Christian Y. Lytle</name><name sortKey="Vullev, Valentine I" sort="Vullev, Valentine I" uniqKey="Vullev V" first="Valentine I" last="Vullev">Valentine I. Vullev</name><name sortKey="Walker, Ameae M" sort="Walker, Ameae M" uniqKey="Walker A" first="Ameae M" last="Walker">Ameae M. Walker</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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