Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin
Identifieur interne : 000A90 ( Main/Exploration ); précédent : 000A89; suivant : 000A91Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin
Auteurs : Alicja Karabasz [Pologne] ; Dorota Lachowicz [Pologne] ; Anna Karewicz [Pologne] ; Renata Mezyk-Kopec [Pologne] ; Krystyna Stali Ska [Pologne] ; Ewa Werner [Pologne] ; Agnieszka Cierniak [Pologne] ; Grzegorz Dyduch [Pologne] ; Joanna Bereta [Pologne] ; Monika Bzowska [Pologne]Source :
- International Journal of Nanomedicine [ 1176-9114 ] ; 2019.
Abstract
Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models.
Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur.
Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas.
The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.
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DOI: 10.2147/IJN.S213942
PubMed: 31564877
PubMed Central: 6735652
Affiliations:
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University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bzowska, Monika" sort="Bzowska, Monika" uniqKey="Bzowska M" first="Monika" last="Bzowska">Monika Bzowska</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31564877</idno><idno type="pmc">6735652</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735652</idno><idno type="RBID">PMC:6735652</idno><idno 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anticancer activity of micelles of sodium alginate-curcumin</title><author><name sortKey="Karabasz, Alicja" sort="Karabasz, Alicja" uniqKey="Karabasz A" first="Alicja" last="Karabasz">Alicja Karabasz</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lachowicz, Dorota" sort="Lachowicz, Dorota" uniqKey="Lachowicz D" first="Dorota" last="Lachowicz">Dorota Lachowicz</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Karewicz, Anna" sort="Karewicz, Anna" uniqKey="Karewicz A" first="Anna" last="Karewicz">Anna Karewicz</name><affiliation wicri:level="1"><nlm:aff id="AFF0003"><institution>Faculty of Chemistry, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mezyk Kopec, Renata" sort="Mezyk Kopec, Renata" uniqKey="Mezyk Kopec R" first="Renata" last="Mezyk-Kopec">Renata Mezyk-Kopec</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stali Ska, Krystyna" sort="Stali Ska, Krystyna" uniqKey="Stali Ska K" first="Krystyna" last="Stali Ska">Krystyna Stali Ska</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Werner, Ewa" sort="Werner, Ewa" uniqKey="Werner E" first="Ewa" last="Werner">Ewa Werner</name><affiliation wicri:level="1"><nlm:aff id="AFF0004"><institution>Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0005"><institution>Department of Animal Reproduction and Anatomy, Faculty of Animal Science, University of Agriculture</institution>,<addr-line>Krakow</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cierniak, Agnieszka" sort="Cierniak, Agnieszka" uniqKey="Cierniak A" first="Agnieszka" last="Cierniak">Agnieszka Cierniak</name><affiliation wicri:level="1"><nlm:aff id="AFF0006"><institution>Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dyduch, Grzegorz" sort="Dyduch, Grzegorz" uniqKey="Dyduch G" first="Grzegorz" last="Dyduch">Grzegorz Dyduch</name><affiliation wicri:level="1"><nlm:aff id="AFF0007"><institution>Department of Pathomorphology, Jagiellonian University Medical College</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bereta, Joanna" sort="Bereta, Joanna" uniqKey="Bereta J" first="Joanna" last="Bereta">Joanna Bereta</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bzowska, Monika" sort="Bzowska, Monika" uniqKey="Bzowska M" first="Monika" last="Bzowska">Monika Bzowska</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University</institution>,<addr-line>Kraków</addr-line>,<country>Poland</country></nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S2001"><title>Background</title><p>Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models.</p></sec><sec id="S2002"><title>Method</title><p>Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur.</p></sec><sec id="S2003"><title>Results</title><p>Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas.</p></sec><sec id="S2004"><title>Conclusion</title><p>The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Pologne</li></country></list><tree><country name="Pologne"><noRegion><name sortKey="Karabasz, Alicja" sort="Karabasz, Alicja" uniqKey="Karabasz A" first="Alicja" last="Karabasz">Alicja Karabasz</name></noRegion><name sortKey="Bereta, Joanna" sort="Bereta, Joanna" uniqKey="Bereta J" first="Joanna" last="Bereta">Joanna Bereta</name><name sortKey="Bzowska, Monika" sort="Bzowska, Monika" uniqKey="Bzowska M" first="Monika" last="Bzowska">Monika Bzowska</name><name sortKey="Cierniak, Agnieszka" sort="Cierniak, Agnieszka" uniqKey="Cierniak A" first="Agnieszka" last="Cierniak">Agnieszka Cierniak</name><name sortKey="Dyduch, Grzegorz" sort="Dyduch, Grzegorz" uniqKey="Dyduch G" first="Grzegorz" last="Dyduch">Grzegorz Dyduch</name><name sortKey="Karewicz, Anna" sort="Karewicz, Anna" uniqKey="Karewicz A" first="Anna" last="Karewicz">Anna Karewicz</name><name sortKey="Lachowicz, Dorota" sort="Lachowicz, Dorota" uniqKey="Lachowicz D" first="Dorota" last="Lachowicz">Dorota Lachowicz</name><name sortKey="Mezyk Kopec, Renata" sort="Mezyk Kopec, Renata" uniqKey="Mezyk Kopec R" first="Renata" last="Mezyk-Kopec">Renata Mezyk-Kopec</name><name sortKey="Stali Ska, Krystyna" sort="Stali Ska, Krystyna" uniqKey="Stali Ska K" first="Krystyna" last="Stali Ska">Krystyna Stali Ska</name><name sortKey="Werner, Ewa" sort="Werner, Ewa" uniqKey="Werner E" first="Ewa" last="Werner">Ewa Werner</name><name sortKey="Werner, Ewa" sort="Werner, Ewa" uniqKey="Werner E" first="Ewa" last="Werner">Ewa Werner</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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