Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective
Identifieur interne : 000138 ( Pmc/Checkpoint ); précédent : 000137; suivant : 000139Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective
Auteurs : Yasamin Davatgaran-Taghipour [Iran] ; Salar Masoomzadeh [Iran] ; Mohammad Hosein Farzaei [Iran] ; Roodabeh Bahramsoltani [Iran] ; Zahra Karimi-Soureh [Iran] ; Roja Rahimi [Iran] ; Mohammad Abdollahi [Iran]Source :
- International Journal of Nanomedicine [ 1176-9114 ] ; 2017.
Abstract
Cancer is defined as the abnormal cell growth that can cause life-threatening malignancies with high financial costs for patients as well as the health care system. Natural polyphenols have long been used for the prevention and treatment of several disorders due to their antioxidant, anti-inflammatory, cytotoxic, antineoplastic, and immunomodulatory effects discussed in the literature; thus, these phytochemicals are potentially able to act as chemopreventive and chemotherapeutic agents in different types of cancer. One of the problems regarding the use of polyphenolic compounds is their low bioavailability. Different types of formulations have been designed for the improvement of bioavailability of these compounds, nanonization being one of the most notable approaches among them. This study aimed to review current data on the nanoformulations of natural polyphenols as chemopreventive and chemotherapeutic agents and to discuss their molecular anticancer mechanisms of action. Nanoformulations of natural polyphenols as bioactive agents, including resveratrol, curcumin, quercetin, epigallocatechin-3-gallate, chrysin, baicalein, luteolin, honokiol, silibinin, and coumarin derivatives, in a dose-dependent manner, result in better efficacy for the prevention and treatment of cancer. The impact of nanoformulation methods for these natural agents on tumor cells has gained wider attention due to improvement in targeted therapy and bioavailability, as well as enhancement of stability. Today, several nanoformulations are designed for delivery of polyphenolic compounds, including nanosuspensions, solid lipid nanoparticles, liposomes, gold nanoparticles, and polymeric nanoparticles, which have resulted in better antineoplastic activity, higher intracellular concentration of polyphenols, slow and sustained release of the drugs, and improvement of proapoptotic activity against tumor cells. To conclude, natural polyphenols demonstrate remarkable anticancer potential in pharmacotherapy; however, the obstacles in terms of their bioavailability in and toxicity to normal cells, as well as targeted drug delivery to malignant cells, can be overcome using nanoformulation-based technologies, which optimize the bioefficacy of these natural drugs.
Url:
DOI: 10.2147/IJN.S131973
PubMed: 28435252
PubMed Central: 5388197
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective</title><author><name sortKey="Davatgaran Taghipour, Yasamin" sort="Davatgaran Taghipour, Yasamin" uniqKey="Davatgaran Taghipour Y" first="Yasamin" last="Davatgaran-Taghipour">Yasamin Davatgaran-Taghipour</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-12-2689">Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijn-12-2689">PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Masoomzadeh, Salar" sort="Masoomzadeh, Salar" uniqKey="Masoomzadeh S" first="Salar" last="Masoomzadeh">Salar Masoomzadeh</name><affiliation wicri:level="1"><nlm:aff id="af3-ijn-12-2689">Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan</wicri:regionArea><wicri:noRegion>Zanjan</wicri:noRegion></affiliation></author><author><name sortKey="Farzaei, Mohammad Hosein" sort="Farzaei, Mohammad Hosein" uniqKey="Farzaei M" first="Mohammad Hosein" last="Farzaei">Mohammad Hosein Farzaei</name><affiliation wicri:level="1"><nlm:aff id="af4-ijn-12-2689">Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah</wicri:regionArea><wicri:noRegion>Kermanshah</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af5-ijn-12-2689">Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah</wicri:regionArea><wicri:noRegion>Kermanshah</wicri:noRegion></affiliation></author><author><name sortKey="Bahramsoltani, Roodabeh" sort="Bahramsoltani, Roodabeh" uniqKey="Bahramsoltani R" first="Roodabeh" last="Bahramsoltani">Roodabeh Bahramsoltani</name><affiliation wicri:level="1"><nlm:aff id="af6-ijn-12-2689">Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Karimi Soureh, Zahra" sort="Karimi Soureh, Zahra" uniqKey="Karimi Soureh Z" first="Zahra" last="Karimi-Soureh">Zahra Karimi-Soureh</name><affiliation wicri:level="1"><nlm:aff id="af7-ijn-12-2689">School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Rahimi, Roja" sort="Rahimi, Roja" uniqKey="Rahimi R" first="Roja" last="Rahimi">Roja Rahimi</name><affiliation wicri:level="1"><nlm:aff id="af6-ijn-12-2689">Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af8-ijn-12-2689">Evidence-Based Medicine Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Evidence-Based Medicine Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Abdollahi, Mohammad" sort="Abdollahi, Mohammad" uniqKey="Abdollahi M" first="Mohammad" last="Abdollahi">Mohammad Abdollahi</name><affiliation wicri:level="1"><nlm:aff id="af9-ijn-12-2689">Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af10-ijn-12-2689">Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical 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clinical perspective</title><author><name sortKey="Davatgaran Taghipour, Yasamin" sort="Davatgaran Taghipour, Yasamin" uniqKey="Davatgaran Taghipour Y" first="Yasamin" last="Davatgaran-Taghipour">Yasamin Davatgaran-Taghipour</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-12-2689">Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijn-12-2689">PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Masoomzadeh, Salar" sort="Masoomzadeh, Salar" uniqKey="Masoomzadeh S" first="Salar" last="Masoomzadeh">Salar Masoomzadeh</name><affiliation wicri:level="1"><nlm:aff id="af3-ijn-12-2689">Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan</wicri:regionArea><wicri:noRegion>Zanjan</wicri:noRegion></affiliation></author><author><name sortKey="Farzaei, Mohammad Hosein" sort="Farzaei, Mohammad Hosein" uniqKey="Farzaei M" first="Mohammad Hosein" last="Farzaei">Mohammad Hosein Farzaei</name><affiliation wicri:level="1"><nlm:aff id="af4-ijn-12-2689">Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah</wicri:regionArea><wicri:noRegion>Kermanshah</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af5-ijn-12-2689">Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah</wicri:regionArea><wicri:noRegion>Kermanshah</wicri:noRegion></affiliation></author><author><name sortKey="Bahramsoltani, Roodabeh" sort="Bahramsoltani, Roodabeh" uniqKey="Bahramsoltani R" first="Roodabeh" last="Bahramsoltani">Roodabeh Bahramsoltani</name><affiliation wicri:level="1"><nlm:aff id="af6-ijn-12-2689">Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Karimi Soureh, Zahra" sort="Karimi Soureh, Zahra" uniqKey="Karimi Soureh Z" first="Zahra" last="Karimi-Soureh">Zahra Karimi-Soureh</name><affiliation wicri:level="1"><nlm:aff id="af7-ijn-12-2689">School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Rahimi, Roja" sort="Rahimi, Roja" uniqKey="Rahimi R" first="Roja" last="Rahimi">Roja Rahimi</name><affiliation wicri:level="1"><nlm:aff id="af6-ijn-12-2689">Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af8-ijn-12-2689">Evidence-Based Medicine Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Evidence-Based Medicine Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Abdollahi, Mohammad" sort="Abdollahi, Mohammad" uniqKey="Abdollahi M" first="Mohammad" last="Abdollahi">Mohammad Abdollahi</name><affiliation wicri:level="1"><nlm:aff id="af9-ijn-12-2689">Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af10-ijn-12-2689">Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</nlm:aff><country xml:lang="fr">Iran</country><wicri:regionArea>Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</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="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Cancer is defined as the abnormal cell growth that can cause life-threatening malignancies with high financial costs for patients as well as the health care system. Natural polyphenols have long been used for the prevention and treatment of several disorders due to their antioxidant, anti-inflammatory, cytotoxic, antineoplastic, and immunomodulatory effects discussed in the literature; thus, these phytochemicals are potentially able to act as chemopreventive and chemotherapeutic agents in different types of cancer. One of the problems regarding the use of polyphenolic compounds is their low bioavailability. Different types of formulations have been designed for the improvement of bioavailability of these compounds, nanonization being one of the most notable approaches among them. This study aimed to review current data on the nanoformulations of natural polyphenols as chemopreventive and chemotherapeutic agents and to discuss their molecular anticancer mechanisms of action. Nanoformulations of natural polyphenols as bioactive agents, including resveratrol, curcumin, quercetin, epigallocatechin-3-gallate, chrysin, baicalein, luteolin, honokiol, silibinin, and coumarin derivatives, in a dose-dependent manner, result in better efficacy for the prevention and treatment of cancer. The impact of nanoformulation methods for these natural agents on tumor cells has gained wider attention due to improvement in targeted therapy and bioavailability, as well as enhancement of stability. Today, several nanoformulations are designed for delivery of polyphenolic compounds, including nanosuspensions, solid lipid nanoparticles, liposomes, gold nanoparticles, and polymeric nanoparticles, which have resulted in better antineoplastic activity, higher intracellular concentration of polyphenols, slow and sustained release of the drugs, and improvement of proapoptotic activity against tumor cells. To conclude, natural polyphenols demonstrate remarkable anticancer potential in pharmacotherapy; however, the obstacles in terms of their bioavailability in and toxicity to normal cells, as well as targeted drug delivery to malignant cells, can be overcome using nanoformulation-based technologies, which optimize the bioefficacy of these natural drugs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ochwang, Do" uniqKey="Ochwang D">DO Ochwang’i</name></author><author><name sortKey="Kimwele, Cn" uniqKey="Kimwele C">CN Kimwele</name></author><author><name sortKey="Oduma, Ja" uniqKey="Oduma J">JA Oduma</name></author><author><name sortKey="Gathumbi, Pk" uniqKey="Gathumbi P">PK Gathumbi</name></author><author><name sortKey="Mbaria, Jm" uniqKey="Mbaria J">JM Mbaria</name></author><author><name sortKey="Kiama, Sg" uniqKey="Kiama S">SG Kiama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jemal, A" 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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-id journal-id-type="publisher-id">International Journal of 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">28435252</article-id><article-id pub-id-type="pmc">5388197</article-id><article-id pub-id-type="doi">10.2147/IJN.S131973</article-id><article-id pub-id-type="publisher-id">ijn-12-2689</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Davatgaran-Taghipour</surname><given-names>Yasamin</given-names></name><xref ref-type="aff" rid="af1-ijn-12-2689">1</xref><xref ref-type="aff" rid="af2-ijn-12-2689">2</xref></contrib><contrib contrib-type="author"><name><surname>Masoomzadeh</surname><given-names>Salar</given-names></name><xref ref-type="aff" rid="af3-ijn-12-2689">3</xref></contrib><contrib contrib-type="author"><name><surname>Farzaei</surname><given-names>Mohammad Hosein</given-names></name><xref ref-type="aff" rid="af4-ijn-12-2689">4</xref><xref ref-type="aff" rid="af5-ijn-12-2689">5</xref></contrib><contrib contrib-type="author"><name><surname>Bahramsoltani</surname><given-names>Roodabeh</given-names></name><xref ref-type="aff" rid="af6-ijn-12-2689">6</xref></contrib><contrib contrib-type="author"><name><surname>Karimi-Soureh</surname><given-names>Zahra</given-names></name><xref ref-type="aff" rid="af7-ijn-12-2689">7</xref></contrib><contrib contrib-type="author"><name><surname>Rahimi</surname><given-names>Roja</given-names></name><xref ref-type="aff" rid="af6-ijn-12-2689">6</xref><xref ref-type="aff" rid="af8-ijn-12-2689">8</xref></contrib><contrib contrib-type="author"><name><surname>Abdollahi</surname><given-names>Mohammad</given-names></name><xref ref-type="aff" rid="af9-ijn-12-2689">9</xref><xref ref-type="aff" rid="af10-ijn-12-2689">10</xref><xref ref-type="corresp" rid="c1-ijn-12-2689"></xref></contrib></contrib-group><aff id="af1-ijn-12-2689"><label>1</label>Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran</aff><aff id="af2-ijn-12-2689"><label>2</label>PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran</aff><aff id="af3-ijn-12-2689"><label>3</label>Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran</aff><aff id="af4-ijn-12-2689"><label>4</label>Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran</aff><aff id="af5-ijn-12-2689"><label>5</label>Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran</aff><aff id="af6-ijn-12-2689"><label>6</label>Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran</aff><aff id="af7-ijn-12-2689"><label>7</label>School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran</aff><aff id="af8-ijn-12-2689"><label>8</label>Evidence-Based Medicine Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</aff><aff id="af9-ijn-12-2689"><label>9</label>Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</aff><aff id="af10-ijn-12-2689"><label>10</label>Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran</aff><author-notes><corresp id="c1-ijn-12-2689">Correspondence: Mohammad Abdollahi, Division of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Keshavarz Bulvard, Ebn-E-Sina Street, Tehran 1417614411, Iran, Email <email>mohammad@tums.ac.ir</email></corresp></author-notes><pub-date pub-type="collection"><year>2017</year></pub-date><pub-date pub-type="epub"><day>04</day><month>4</month><year>2017</year></pub-date><volume>12</volume><fpage>2689</fpage><lpage>2702</lpage><permissions><copyright-statement>© 2017 Davatgaran-Taghipour et al. This work is published and licensed by Dove Medical Press Limited</copyright-statement><copyright-year>2017</copyright-year><license><license-p>The full terms of this license are available at <ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link> and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.</license-p></license></permissions><abstract><p>Cancer is defined as the abnormal cell growth that can cause life-threatening malignancies with high financial costs for patients as well as the health care system. Natural polyphenols have long been used for the prevention and treatment of several disorders due to their antioxidant, anti-inflammatory, cytotoxic, antineoplastic, and immunomodulatory effects discussed in the literature; thus, these phytochemicals are potentially able to act as chemopreventive and chemotherapeutic agents in different types of cancer. One of the problems regarding the use of polyphenolic compounds is their low bioavailability. Different types of formulations have been designed for the improvement of bioavailability of these compounds, nanonization being one of the most notable approaches among them. This study aimed to review current data on the nanoformulations of natural polyphenols as chemopreventive and chemotherapeutic agents and to discuss their molecular anticancer mechanisms of action. Nanoformulations of natural polyphenols as bioactive agents, including resveratrol, curcumin, quercetin, epigallocatechin-3-gallate, chrysin, baicalein, luteolin, honokiol, silibinin, and coumarin derivatives, in a dose-dependent manner, result in better efficacy for the prevention and treatment of cancer. The impact of nanoformulation methods for these natural agents on tumor cells has gained wider attention due to improvement in targeted therapy and bioavailability, as well as enhancement of stability. Today, several nanoformulations are designed for delivery of polyphenolic compounds, including nanosuspensions, solid lipid nanoparticles, liposomes, gold nanoparticles, and polymeric nanoparticles, which have resulted in better antineoplastic activity, higher intracellular concentration of polyphenols, slow and sustained release of the drugs, and improvement of proapoptotic activity against tumor cells. To conclude, natural polyphenols demonstrate remarkable anticancer potential in pharmacotherapy; however, the obstacles in terms of their bioavailability in and toxicity to normal cells, as well as targeted drug delivery to malignant cells, can be overcome using nanoformulation-based technologies, which optimize the bioefficacy of these natural drugs.</p></abstract><kwd-group><title>Keywords</title><kwd>natural products</kwd><kwd>flavonoid</kwd><kwd>anthocyanin</kwd><kwd>tumor</kwd><kwd>malignancy</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-ijn-12-2689" position="float"><label>Figure 1</label><caption><p>Polyphenol nanoformulations and their mechanisms as antineoplastic agents.</p><p><bold>Abbreviations:</bold> Casp-3 and -9, caspase-3 and caspase-9; MAPK/ERK, mitogen-activated protein kinases/extracellular signal-regulated kinases.</p></caption><graphic xlink:href="ijn-12-2689Fig1"></graphic></fig><table-wrap id="t1-ijn-12-2689" position="float"><label>Table 1</label><caption><p>Polyphenols with anticancer activity and their mechanisms of action</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="top" align="left" rowspan="1" colspan="1">Phytochemical category</th><th valign="top" align="left" rowspan="1" colspan="1">Phytochemical name</th><th valign="top" align="left" rowspan="1" colspan="1">Nanoformulation</th><th valign="top" align="left" rowspan="1" colspan="1">Cell line/animal model</th><th valign="top" align="left" rowspan="1" colspan="1">Anticancer activity</th><th valign="top" align="left" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td rowspan="2" valign="top" align="left" colspan="1">Coumarin</td><td valign="top" align="left" rowspan="1" colspan="1">4-Methyl-7-hydroxy coumarin<break></break><graphic xlink:href="ijn-12-2689Fig2"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">PLGA nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Melanoma A375 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell viability<break></break>↑ Apoptosis<break></break>↑DNA fragmentation<break></break>↑Caspase-3 and p53</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b34-ijn-12-2689" ref-type="bibr">34</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Farnesiferol C<break></break><graphic xlink:href="ijn-12-2689Fig3"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Dendrosomal nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">AGS gastric cancer cell line</td><td valign="top" align="left" rowspan="1" colspan="1">↓Proliferation<break></break>↑Expression ratio of Bax/Bcl-2</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b35-ijn-12-2689" ref-type="bibr">35</xref></td></tr><tr><td rowspan="13" valign="top" align="left" colspan="1">Diarylheptanoid</td><td rowspan="13" valign="top" align="left" colspan="1">Curcumin
<graphic xlink:href="ijn-12-2689Fig4"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">PLGA nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">CaSki and SiHa cervical cancer cells<break></break>Orthotopic mouse model of cervical cancer</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell growth<break></break>↑Apoptosis and Gl/S cell cycle arrest<break></break>↓miRNA-2, nuclear β-catenin and E6/E7 HPV oncoproteins</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b37-ijn-12-2689" ref-type="bibr">37</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">MPEG-PLA-PAE nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human breast cancer MCF-7 cells<break></break>MCF-7 tumor-bearing mice</td><td valign="top" align="left" rowspan="1" colspan="1">↑Curcumin uptake<break></break>↓Cell growth<break></break>↓Tumor growth in vivo</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b45-ijn-12-2689" ref-type="bibr">45</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PLGA nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Cisplatin-resistant A2780CP ovarian cancer cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Bcl-XL and Mcl-l<break></break>↓Cell growth<break></break>↑Apoptosis</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b43-ijn-12-2689" ref-type="bibr">43</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PLGA nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human colorectal cancer HCT116 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Apoptosis by G2/M phase cell cycle arrest<break></break>↓Cell viability<break></break>↓Toxicity for normal cells</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b41-ijn-12-2689" ref-type="bibr">41</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PLGA nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Cisplatin-resistant A2780CP ovarian cancer and metastatic MDA-MB-231 breast cancer cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Apoptosis<break></break>↓Proliferation and colony formation</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b42-ijn-12-2689" ref-type="bibr">42</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PNIPAAm-COOH nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human prostate cancer PC3, human breast cancer MCF-7 cells, and human nasopharyngeal cancer KB cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Curcumin uptake<break></break>↓Cell viability in cancerous cells but not in normal cells<break></break>↑Apoptosis in PC3 cells<break></break>↓Mitochondrial membrane potential in PC3 cells</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b46-ijn-12-2689" ref-type="bibr">46</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Cyclodextrin/cellulose nanocrystals</td><td valign="top" align="left" rowspan="1" colspan="1">Human prostate cancer PC-3 and DU145, as well as human colorectal carcinoma HT-29 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Curcumin uptake<break></break>↓Proliferation</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b47-ijn-12-2689" ref-type="bibr">47</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Folate-modified PLA-PEG micelles</td><td valign="top" align="left" rowspan="1" colspan="1">Human hepatocellular carcinoma HepG2 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell growth</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b23-ijn-12-2689" ref-type="bibr">23</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PLGA nanoparticles by conjugation with anti-P-glycoprotein</td><td valign="top" align="left" rowspan="1" colspan="1">Human cervical carcinoma KB-VI and KB-3-1 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Curcumin uptake<break></break>↓Cell viability</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b44-ijn-12-2689" ref-type="bibr">44</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Dextran micelles</td><td valign="top" align="left" rowspan="1" colspan="1">C6 glioma cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Curcumin uptake<break></break>↓Cell viability</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b107-ijn-12-2689" ref-type="bibr">107</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Dendrosomal nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">BALB/c metastatic breast cancer in mice</td><td valign="top" align="left" rowspan="1" colspan="1">↓Tumor size<break></break>↓<italic>STAT3</italic>, <italic>IL-10</italic>, and arginase 1 gene expression<break></break>↑<italic>STAT4</italic> and <italic>IL-12</italic> gene expression</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b48-ijn-12-2689" ref-type="bibr">48</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">F68-Cis-curcumin conjugate micelles</td><td valign="top" align="left" rowspan="1" colspan="1">Human ovarian carcinoma A2780 and hepatocellular carcinoma SMMC 7721 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓MMP<break></break>↑Curcumin cellular uptake<break></break>↑Apoptosis</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b106-ijn-12-2689" ref-type="bibr">106</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PLGA nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Diethylnitrosamine-induced hepatocellular carcinoma in Swiss albino rat</td><td valign="top" align="left" rowspan="1" colspan="1">↑Apoptosis<break></break>↓Mitochondrial ROS generation<break></break>↑GSH, SOD, and CAT<break></break>↑Mitochondrial cyt c release<break></break>↓iNOS<break></break>↓ALP, AST, and ALT</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b108-ijn-12-2689" ref-type="bibr">108</xref></td></tr><tr><td rowspan="7" valign="top" align="left" colspan="1"></td><td rowspan="7" valign="top" align="left" colspan="1"></td><td valign="top" align="left" rowspan="1" colspan="1">PCL nanodroplets</td><td valign="top" align="left" rowspan="1" colspan="1">S180 cancer-bearing mice</td><td valign="top" align="left" rowspan="1" colspan="1">↓Tumor growth</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b49-ijn-12-2689" ref-type="bibr">49</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PHEMA nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Ovarian cancer SKOV-3 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Tumor growth<break></break>↑Apoptosis</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b109-ijn-12-2689" ref-type="bibr">109</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Colloidal nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Esophageal Barrett cancer OE19 and OE33 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Proliferation in cancerous cells but not in normal cells<break></break>No significant effect on apoptosis<break></break>↓Activated T-cell apoptosis and production of TNF-α, IL-8, IL-6, IL-10, and IL-Iβ</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b110-ijn-12-2689" ref-type="bibr">110</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Nanoparticles prepared by ultrasonic spray</td><td valign="top" align="left" rowspan="1" colspan="1">Human embyronic kidney HEK and human PC3 prostate cancer cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell viability (more obvious on HEK cells)</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b51-ijn-12-2689" ref-type="bibr">51</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Nanostructured lipid carriers</td><td valign="top" align="left" rowspan="1" colspan="1">Human neuroblastoma LAN5 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell viability<break></break>↑Hsp70</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b52-ijn-12-2689" ref-type="bibr">52</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Polymer–coated magnetic nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human ovarian carcinoma SKOv-3 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell viability</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b53-ijn-12-2689" ref-type="bibr">53</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Lipid-polymer hybrid nanoparticles in combination with docetaxel</td><td valign="top" align="left" rowspan="1" colspan="1">Human PC3 prostate adenocarcinoma cells, BALB/c nude mice</td><td valign="top" align="left" rowspan="1" colspan="1">↑Adherence ability of the nanocarriers to cell membrane in PC3<break></break>↑Antitumor effects in PC3<break></break>↓Tumor growth in vivo</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b54-ijn-12-2689" ref-type="bibr">54</xref></td></tr><tr><td rowspan="10" valign="top" align="left" colspan="1">Flavonoid</td><td valign="top" align="left" rowspan="1" colspan="1">Baicalein
<graphic xlink:href="ijn-12-2689Fig5"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Paclitaxel–baicalein dual-targeted ligands of folate and hyaluronic acid</td><td valign="top" align="left" rowspan="1" colspan="1">Human lung cancer A549 and drug-resistant lung cancer A549/PTX cells, xenograft mouse model of A549/PTX drug-resistant human lung cancer</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell viability<break></break>↓Tumor growth in vivo</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b82-ijn-12-2689" ref-type="bibr">82</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Chrysin
<graphic xlink:href="ijn-12-2689Fig6"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Nanosuspension</td><td valign="top" align="left" rowspan="1" colspan="1">Human hepatocellular carcinoma HepG2 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell growth</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b85-ijn-12-2689" ref-type="bibr">85</xref></td></tr><tr><td rowspan="2" valign="top" align="left" colspan="1">EGCG
<graphic xlink:href="ijn-12-2689Fig7"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Ca/AlNO<sub>3</sub>-layered double-hydroxide nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human prostate cancer PC-3 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Apoptosis<break></break>↓Cell viability<break></break>↓Colony formation</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b87-ijn-12-2689" ref-type="bibr">87</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Chitosan nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human melanoma Mel 928 cells, xenograft athymic nu/nu mouse model of melanoma</td><td valign="top" align="left" rowspan="1" colspan="1">↓Apoptosis<break></break>↓Cell viability<break></break>↑Bax<break></break>↓Bcl-2<break></break>↓Caspase-3 and caspase-9 protein expression<break></break>↑Cleaved caspase-9<break></break>↑PARP cleavage<break></break>G2/M phase cell cycle arrest<break></break>Induction of p21 and p27<break></break>Inhibition of cyclin DI and D3<break></break>↓Tumor growth and proliferation in vivo<break></break>Inhibition of CDK 4 and 6<break></break>↑Apoptosis</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b88-ijn-12-2689" ref-type="bibr">88</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">EGCG (+ paclitaxel)</td><td valign="top" align="left" rowspan="1" colspan="1">Core–shell PLGA–casein nanoparticles in targeted and nontargeted form</td><td valign="top" align="left" rowspan="1" colspan="1">Human breast cancer MDA-MB-231 and MCF-7 cells, breast cancer cells isolated from patients</td><td valign="top" align="left" rowspan="1" colspan="1">↑Apoptosis<break></break>↓NF-κB activation<break></break>Anticancer effects on patients samples</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b89-ijn-12-2689" ref-type="bibr">89</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Green tea polyphenols</td><td valign="top" align="left" rowspan="1" colspan="1">Graphene nanosheets</td><td valign="top" align="left" rowspan="1" colspan="1">Colon cancer HT29 and Sw48 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Photothermal destruction of Sw48</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b90-ijn-12-2689" ref-type="bibr">90</xref></td></tr><tr><td rowspan="2" valign="top" align="left" colspan="1">Luteolin
<graphic xlink:href="ijn-12-2689Fig8"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Phytosome</td><td valign="top" align="left" rowspan="1" colspan="1">Human MDA-MB-231 breast cancer cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell viability<break></break>↑<italic>Nrf2 and related downstream genes HoI</italic> and <italic>MDRI</italic><break></break><italic>↑Sensitivity to doxorubicin</italic></td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b92-ijn-12-2689" ref-type="bibr">92</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PLA-PEG-OMe nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Lung cancer H292 cells, squamous cell carcinoma of head-and-neck Tu212 cells, xenograft mouse model of head and neck cancer</td><td valign="top" align="left" rowspan="1" colspan="1">↓Tumor growth<break></break>↓Colony formation<break></break>↓Tumor size in animals</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b93-ijn-12-2689" ref-type="bibr">93</xref></td></tr><tr><td rowspan="2" valign="top" align="left" colspan="1">Quercetin
<graphic xlink:href="ijn-12-2689Fig9"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Phytosome</td><td valign="top" align="left" rowspan="1" colspan="1">Human breast cancer MCF-7 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Apoptosis<break></break>No significant change in <italic>Nrf2</italic><break></break><italic>↓mRNA expression of Nrf2</italic> downstream genes <italic>NQOI</italic> and <italic>MRPi</italic></td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b95-ijn-12-2689" ref-type="bibr">95</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Liposome</td><td valign="top" align="left" rowspan="1" colspan="1">Human breast cancer MCF-7 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell proliferation<break></break>↑Antitoxic effect</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b96-ijn-12-2689" ref-type="bibr">96</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Flavonolignan</td><td valign="top" align="left" rowspan="1" colspan="1">Silibinin (+ glycyrrhizic acid)
<graphic xlink:href="ijn-12-2689Fig10"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Pegylated nanoliposomes</td><td valign="top" align="left" rowspan="1" colspan="1">Human hepatocellular carcinoma HepG2 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Cell viability in cancerous cells but not in normal cells</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b55-ijn-12-2689" ref-type="bibr">55</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Lignan</td><td valign="top" align="left" rowspan="1" colspan="1">Honokiol
<graphic xlink:href="ijn-12-2689Fig11"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">MPEG micelles</td><td valign="top" align="left" rowspan="1" colspan="1">Mouse Lewis lung cancer cell lines LL/2</td><td valign="top" align="left" rowspan="1" colspan="1">↓Cell growth<break></break>Induction of cell cycle arrest in G0/G1 phase</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b60-ijn-12-2689" ref-type="bibr">60</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Naphthoquinone</td><td valign="top" align="left" rowspan="1" colspan="1">Plumbagin
<graphic xlink:href="ijn-12-2689Fig12"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">Silver nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human skin HaCaT and A431 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Pyruvate kinase activity (more obvious in A431)<break></break>↑Apoptosis by production of free radicals</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b66-ijn-12-2689" ref-type="bibr">66</xref></td></tr><tr><td rowspan="5" valign="top" align="left" colspan="1">Stilbene</td><td rowspan="5" valign="top" align="left" colspan="1">Resveratrol
<graphic xlink:href="ijn-12-2689Fig13"></graphic></td><td valign="top" align="left" rowspan="1" colspan="1">PLGA-PEG-COOH nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human prostate cancer DU-145, PC-3, and LNCaP cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Cell growth and proliferation</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b68-ijn-12-2689" ref-type="bibr">68</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">PCL nanocapsules<break></break>MPEG-PCL nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Murine melanoma B16F10 cells<break></break>Rat C6 glioma cells</td><td valign="top" align="left" rowspan="1" colspan="1">↓Tumor growth<break></break>↓Cell viability</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b69-ijn-12-2689" ref-type="bibr">69</xref><break></break><xref rid="b70-ijn-12-2689" ref-type="bibr">70</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Pegylated coencapsulation with 5-FU</td><td valign="top" align="left" rowspan="1" colspan="1">Human NT8e head and neck cancer</td><td valign="top" align="left" rowspan="1" colspan="1">Synergistic antineoplastic effect at high concentrations and antagonistic effect at low concentrations of resveratrol<break></break>↑Bax<break></break>↑Bcl-2</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b72-ijn-12-2689" ref-type="bibr">72</xref></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Bovine serum albumin<break></break>Nanoparticles</td><td valign="top" align="left" rowspan="1" colspan="1">Human ovarian cancer SKOV3 cells</td><td valign="top" align="left" rowspan="1" colspan="1">↑Apoptosis<break></break>↑Bax<break></break>↑DNA fragmentation<break></break>↑Cyt <italic>c</italic> and apoptosis-inducing factor release</td><td valign="top" align="left" rowspan="1" colspan="1"><xref rid="b71-ijn-12-2689" ref-type="bibr">71</xref></td></tr></tbody></table><table-wrap-foot><fn id="tfn1-ijn-12-2689"><p><bold>Abbreviations:</bold> ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CAT, catalase; cyt c, cytochrome c; 5-FU, 5-fluorouracil; GSH, glutathione; HPV, human papillomavirus; IL, interleukin; iNOS, inducible nitric oxide synthase; miRNA, microRNA; MMP, mitochondrial membrane potential; MPEG, methoxy polyethylene glycol; MPEG-PLA-PAE, (MPEG)-poly(lactide)-poly(b-amino ester); OMe, methoxy group; PAE, poly(b-amino ester); PARP, poly(ADP-ribose) polymerase; PCL, poly(ε-caprolactone); PEG, polyethylene glycol; pegylated, conjugated with PEG; PHEMA, poly(2-hydroxyethyl methacrylate); PLA, polylactic acid; PLGA, poly(lactic-<italic>co</italic>-glycolic acid); PNIPAAm, poly(<italic>N</italic>-isopropylacrylamide); ROS, reactive oxygen species; SOD, superoxide dismutase; TNF, tumor necrosis factor.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t2-ijn-12-2689" position="float"><label>Table 2</label><caption><p>Advantages and disadvantages of conventional formulations versus nanoformulations</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="2" valign="top" align="left" rowspan="1">Nanoformulations
<hr></hr></th><th colspan="2" valign="top" align="left" rowspan="1">Conventional formulations
<hr></hr></th></tr><tr><th valign="top" align="left" rowspan="1" colspan="1">Advantages</th><th valign="top" align="left" rowspan="1" colspan="1">Disadvantages</th><th valign="top" align="left" rowspan="1" colspan="1">Advantages</th><th valign="top" align="left" rowspan="1" colspan="1">Disadvantages</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">Higher surface area-to-volume ratio</td><td valign="top" align="left" rowspan="1" colspan="1">Short shelf life<break></break>Unpredictable toxicity, stability, and pharmacokinetics</td><td valign="top" align="left" rowspan="1" colspan="1">Specified safety profile, predictable toxicity, stability, and pharmacokinetics</td><td valign="top" align="left" rowspan="1" colspan="1">Untargeted drug delivery<break></break>Uncontrollable release</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Improved bioavailability<break></break>Targeted drug delivery<break></break>Sustained drug release</td><td valign="top" align="left" rowspan="1" colspan="1">More expensive</td><td valign="top" align="left" rowspan="1" colspan="1">Less expensive</td><td valign="top" align="left" rowspan="1" colspan="1">Undesirable pharmacokinetics</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Iran</li></country></list><tree><country name="Iran"><noRegion><name sortKey="Davatgaran Taghipour, Yasamin" sort="Davatgaran Taghipour, Yasamin" uniqKey="Davatgaran Taghipour Y" first="Yasamin" last="Davatgaran-Taghipour">Yasamin Davatgaran-Taghipour</name></noRegion><name sortKey="Abdollahi, Mohammad" sort="Abdollahi, Mohammad" uniqKey="Abdollahi M" first="Mohammad" last="Abdollahi">Mohammad Abdollahi</name><name sortKey="Abdollahi, Mohammad" sort="Abdollahi, Mohammad" uniqKey="Abdollahi M" first="Mohammad" last="Abdollahi">Mohammad Abdollahi</name><name sortKey="Bahramsoltani, Roodabeh" sort="Bahramsoltani, Roodabeh" uniqKey="Bahramsoltani R" first="Roodabeh" last="Bahramsoltani">Roodabeh Bahramsoltani</name><name sortKey="Davatgaran Taghipour, Yasamin" sort="Davatgaran Taghipour, Yasamin" uniqKey="Davatgaran Taghipour Y" first="Yasamin" last="Davatgaran-Taghipour">Yasamin Davatgaran-Taghipour</name><name sortKey="Farzaei, Mohammad Hosein" sort="Farzaei, Mohammad Hosein" uniqKey="Farzaei M" first="Mohammad Hosein" last="Farzaei">Mohammad Hosein Farzaei</name><name sortKey="Farzaei, Mohammad Hosein" sort="Farzaei, Mohammad Hosein" uniqKey="Farzaei M" first="Mohammad Hosein" last="Farzaei">Mohammad Hosein Farzaei</name><name sortKey="Karimi Soureh, Zahra" sort="Karimi Soureh, Zahra" uniqKey="Karimi Soureh Z" first="Zahra" last="Karimi-Soureh">Zahra Karimi-Soureh</name><name sortKey="Masoomzadeh, Salar" sort="Masoomzadeh, Salar" uniqKey="Masoomzadeh S" first="Salar" last="Masoomzadeh">Salar Masoomzadeh</name><name sortKey="Rahimi, Roja" sort="Rahimi, Roja" uniqKey="Rahimi R" first="Roja" last="Rahimi">Roja Rahimi</name><name sortKey="Rahimi, Roja" sort="Rahimi, Roja" uniqKey="Rahimi R" first="Roja" last="Rahimi">Roja Rahimi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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