Flower-like curcumin-loaded folic acid-conjugated ZnO-MPA- βcyclodextrin nanostructures enhanced anticancer activity and cellular uptake of curcumin in breast cancer cells
Non-spherical structures are beneficial to advance drug delivery effectiveness compared with common spherical ones, due to increased drug loading capability, improved bonding to a vascular wall, enhanced cellular uptake efficacy and prolonged circulation times. In this study, flower-like Zinc oxide-...
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| Veröffentlicht in: | Materials Science & Engineering C 2019-10, Vol.103, p.109827, Article 109827 |
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| creator | Ghaffari, Seyed-Behnam Sarrafzadeh, Mohammad-Hossein Fakhroueian, Zahra Khorramizadeh, M.Reza |
| description | Non-spherical structures are beneficial to advance drug delivery effectiveness compared with common spherical ones, due to increased drug loading capability, improved bonding to a vascular wall, enhanced cellular uptake efficacy and prolonged circulation times. In this study, flower-like Zinc oxide-βcyclodextrin (βCD) nanostructures functionalized by 3-mercaptopropionic acid (MPA) as a non-spherical delivery system was successfully synthesized for aqueous delivery of curcumin (CUR) to enhance its targeting, bioavailability, and release profile. Terminal carboxyl functional groups were used for the conjugation of folic acid (FA) with the aim of active targeting to folate overexpressing breast cancer cells. The in vitro experimental study and mathematical modeling of CUR release revealed a sustained release with Fickian diffusion as the major release mechanism. MTT, colony formation and Annexin-V FITC/PI assays showed the superior anticancer effect of the system compared to free CUR against breast cancer cell line MDA-MB-231 by promoting the apoptotic respond with no cytotoxic effect on HEK293 normal cells. The efficacy of targeting strategy with FA moieties was demonstrated using the augmented cellular uptake of the FA-conjugated system on overexpressed folate receptor alpha (FRα) cells (MDA-MB-468 breast cancer cell line). Furthermore, loading of CUR to the delivery systems significantly lowered the MIC values (2.5 to 5-fold) against S. aureus and E. coli the infections of which are serious problems in cancer patients. According to the results of this study, the system can serve as a promising non-spherical delivery vehicle for enhancing bioavailability and targeting of hydrophobic anticancer agents in the future.
[Display omitted]
•A non-spherical multi-functional system for targeted cancer therapy was developed.•The system composed of a ZnO-βCD flower-like core functionalized by MPA molecules.•The system showed a sustained drug release with the Fickian diffusion mechanism.•The system showed superior selective apoptosis-induced anticancer effect in MDA-MB-231.•Folic acid conjugation enhanced cellular uptake of curcumin in MDA-MB-468. |
| doi_str_mv | 10.1016/j.msec.2019.109827 |
| format | Article |
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[Display omitted]
•A non-spherical multi-functional system for targeted cancer therapy was developed.•The system composed of a ZnO-βCD flower-like core functionalized by MPA molecules.•The system showed a sustained drug release with the Fickian diffusion mechanism.•The system showed superior selective apoptosis-induced anticancer effect in MDA-MB-231.•Folic acid conjugation enhanced cellular uptake of curcumin in MDA-MB-468.</description><identifier>ISSN: 0928-4931</identifier><identifier>EISSN: 1873-0191</identifier><identifier>DOI: 10.1016/j.msec.2019.109827</identifier><identifier>PMID: 31349522</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>3-Mercaptopropionic Acid - chemistry ; 3-Mercaptopropionic Acid - pharmacology ; Anticancer properties ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antitumor activity ; Antitumor agents ; Apoptosis ; Apoptosis - drug effects ; beta-Cyclodextrins - chemistry ; beta-Cyclodextrins - pharmacology ; Bioavailability ; Biotechnology ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - microbiology ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Cellular structure ; Conjugation ; Controlled release ; Curcumin ; Curcumin - chemistry ; Curcumin - pharmacology ; Cytotoxicity ; Drug Carriers - chemistry ; Drug Carriers - pharmacology ; Drug delivery ; Drug delivery systems ; E coli ; Escherichia coli - growth & development ; Escherichia coli Infections - drug therapy ; Escherichia coli Infections - metabolism ; Escherichia coli Infections - pathology ; Female ; Folic acid ; Folic Acid - pharmacology ; Folic acid receptor targeting ; Functional groups ; HEK293 Cells ; Humans ; Hydrophobicity ; Materials science ; Mathematical models ; Minimum inhibitory concentration ; Nanostructure ; Nanostructures - chemistry ; Nanostructures - therapeutic use ; Non-spherical drug delivery systems ; Staphylococcal Infections - drug therapy ; Staphylococcal Infections - metabolism ; Staphylococcal Infections - pathology ; Staphylococcus aureus - growth & development ; Sustained release ; Zinc ; Zinc oxide ; Zinc Oxide - chemistry ; Zinc Oxide - pharmacology ; Zinc oxide nanostructures ; Zinc oxides</subject><ispartof>Materials Science & Engineering C, 2019-10, Vol.103, p.109827, Article 109827</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Oct 2019</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-41cea9eadbfe06f339229c49f9fed6d213de756731d906af599e3bd216a1facf3</citedby><cites>FETCH-LOGICAL-c384t-41cea9eadbfe06f339229c49f9fed6d213de756731d906af599e3bd216a1facf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0928493119308872$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31349522$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghaffari, Seyed-Behnam</creatorcontrib><creatorcontrib>Sarrafzadeh, Mohammad-Hossein</creatorcontrib><creatorcontrib>Fakhroueian, Zahra</creatorcontrib><creatorcontrib>Khorramizadeh, M.Reza</creatorcontrib><title>Flower-like curcumin-loaded folic acid-conjugated ZnO-MPA- βcyclodextrin nanostructures enhanced anticancer activity and cellular uptake of curcumin in breast cancer cells</title><title>Materials Science & Engineering C</title><addtitle>Mater Sci Eng C Mater Biol Appl</addtitle><description>Non-spherical structures are beneficial to advance drug delivery effectiveness compared with common spherical ones, due to increased drug loading capability, improved bonding to a vascular wall, enhanced cellular uptake efficacy and prolonged circulation times. In this study, flower-like Zinc oxide-βcyclodextrin (βCD) nanostructures functionalized by 3-mercaptopropionic acid (MPA) as a non-spherical delivery system was successfully synthesized for aqueous delivery of curcumin (CUR) to enhance its targeting, bioavailability, and release profile. Terminal carboxyl functional groups were used for the conjugation of folic acid (FA) with the aim of active targeting to folate overexpressing breast cancer cells. The in vitro experimental study and mathematical modeling of CUR release revealed a sustained release with Fickian diffusion as the major release mechanism. MTT, colony formation and Annexin-V FITC/PI assays showed the superior anticancer effect of the system compared to free CUR against breast cancer cell line MDA-MB-231 by promoting the apoptotic respond with no cytotoxic effect on HEK293 normal cells. The efficacy of targeting strategy with FA moieties was demonstrated using the augmented cellular uptake of the FA-conjugated system on overexpressed folate receptor alpha (FRα) cells (MDA-MB-468 breast cancer cell line). Furthermore, loading of CUR to the delivery systems significantly lowered the MIC values (2.5 to 5-fold) against S. aureus and E. coli the infections of which are serious problems in cancer patients. According to the results of this study, the system can serve as a promising non-spherical delivery vehicle for enhancing bioavailability and targeting of hydrophobic anticancer agents in the future.
[Display omitted]
•A non-spherical multi-functional system for targeted cancer therapy was developed.•The system composed of a ZnO-βCD flower-like core functionalized by MPA molecules.•The system showed a sustained drug release with the Fickian diffusion mechanism.•The system showed superior selective apoptosis-induced anticancer effect in MDA-MB-231.•Folic acid conjugation enhanced cellular uptake of curcumin in MDA-MB-468.</description><subject>3-Mercaptopropionic Acid - chemistry</subject><subject>3-Mercaptopropionic Acid - pharmacology</subject><subject>Anticancer properties</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor activity</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>beta-Cyclodextrins - chemistry</subject><subject>beta-Cyclodextrins - pharmacology</subject><subject>Bioavailability</subject><subject>Biotechnology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - microbiology</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cellular structure</subject><subject>Conjugation</subject><subject>Controlled release</subject><subject>Curcumin</subject><subject>Curcumin - chemistry</subject><subject>Curcumin - pharmacology</subject><subject>Cytotoxicity</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Carriers - pharmacology</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>E coli</subject><subject>Escherichia coli - growth & development</subject><subject>Escherichia coli Infections - drug therapy</subject><subject>Escherichia coli Infections - metabolism</subject><subject>Escherichia coli Infections - pathology</subject><subject>Female</subject><subject>Folic acid</subject><subject>Folic Acid - pharmacology</subject><subject>Folic acid receptor targeting</subject><subject>Functional groups</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Hydrophobicity</subject><subject>Materials science</subject><subject>Mathematical models</subject><subject>Minimum inhibitory concentration</subject><subject>Nanostructure</subject><subject>Nanostructures - chemistry</subject><subject>Nanostructures - therapeutic use</subject><subject>Non-spherical drug delivery systems</subject><subject>Staphylococcal Infections - drug therapy</subject><subject>Staphylococcal Infections - metabolism</subject><subject>Staphylococcal Infections - pathology</subject><subject>Staphylococcus aureus - growth & development</subject><subject>Sustained release</subject><subject>Zinc</subject><subject>Zinc oxide</subject><subject>Zinc Oxide - chemistry</subject><subject>Zinc Oxide - pharmacology</subject><subject>Zinc oxide nanostructures</subject><subject>Zinc oxides</subject><issn>0928-4931</issn><issn>1873-0191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2KFDEUhYMoTjv6Ai4k4DptfqqrKuBmGGZUGBkXunET0smNpqxO2vyM9ju58kF8JlN0O0shkHD4zrlJDkLPGV0zyvpX03qXwaw5ZbIJcuTDA7Ri4yBIU9hDtKKSj6STgp2hJzlPlPajGPhjdCaY6OSG8xX6dT3HH5DI7L8BNjWZuvOBzFFbsNjF2RusjbfExDDVL7o09XO4Je8_XBD857c5mDla-FmSDzjoEHNJ1ZSaIGMIX3UwjdeheLMcU4sq_s6XQ9MsNjDPddYJ133RbXp09xfAbW0T6FzwybnA-Sl65PSc4dlpP0efrq8-Xr4lN7dv3l1e3BAjxq6QjhnQErTdOqC9E0JyLk0nnXRge8uZsDBs-kEwK2mv3UZKENum95o5bZw4Ry-PufsUv1fIRU2xptBGKs5HuqGUdbxR_EiZFHNO4NQ--Z1OB8WoWgpSk1oKUktB6lhQM704RdftDuy95V8jDXh9BKA98M5DUtl4WD7SJzBF2ej_l_8X_nenDg</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Ghaffari, Seyed-Behnam</creator><creator>Sarrafzadeh, Mohammad-Hossein</creator><creator>Fakhroueian, Zahra</creator><creator>Khorramizadeh, M.Reza</creator><general>Elsevier B.V</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope></search><sort><creationdate>201910</creationdate><title>Flower-like curcumin-loaded folic acid-conjugated ZnO-MPA- βcyclodextrin nanostructures enhanced anticancer activity and cellular uptake of curcumin in breast cancer cells</title><author>Ghaffari, Seyed-Behnam ; Sarrafzadeh, Mohammad-Hossein ; Fakhroueian, Zahra ; Khorramizadeh, M.Reza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-41cea9eadbfe06f339229c49f9fed6d213de756731d906af599e3bd216a1facf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>3-Mercaptopropionic Acid - 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In this study, flower-like Zinc oxide-βcyclodextrin (βCD) nanostructures functionalized by 3-mercaptopropionic acid (MPA) as a non-spherical delivery system was successfully synthesized for aqueous delivery of curcumin (CUR) to enhance its targeting, bioavailability, and release profile. Terminal carboxyl functional groups were used for the conjugation of folic acid (FA) with the aim of active targeting to folate overexpressing breast cancer cells. The in vitro experimental study and mathematical modeling of CUR release revealed a sustained release with Fickian diffusion as the major release mechanism. MTT, colony formation and Annexin-V FITC/PI assays showed the superior anticancer effect of the system compared to free CUR against breast cancer cell line MDA-MB-231 by promoting the apoptotic respond with no cytotoxic effect on HEK293 normal cells. The efficacy of targeting strategy with FA moieties was demonstrated using the augmented cellular uptake of the FA-conjugated system on overexpressed folate receptor alpha (FRα) cells (MDA-MB-468 breast cancer cell line). Furthermore, loading of CUR to the delivery systems significantly lowered the MIC values (2.5 to 5-fold) against S. aureus and E. coli the infections of which are serious problems in cancer patients. According to the results of this study, the system can serve as a promising non-spherical delivery vehicle for enhancing bioavailability and targeting of hydrophobic anticancer agents in the future.
[Display omitted]
•A non-spherical multi-functional system for targeted cancer therapy was developed.•The system composed of a ZnO-βCD flower-like core functionalized by MPA molecules.•The system showed a sustained drug release with the Fickian diffusion mechanism.•The system showed superior selective apoptosis-induced anticancer effect in MDA-MB-231.•Folic acid conjugation enhanced cellular uptake of curcumin in MDA-MB-468.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31349522</pmid><doi>10.1016/j.msec.2019.109827</doi></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 3-Mercaptopropionic Acid - chemistry 3-Mercaptopropionic Acid - pharmacology Anticancer properties Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antitumor activity Antitumor agents Apoptosis Apoptosis - drug effects beta-Cyclodextrins - chemistry beta-Cyclodextrins - pharmacology Bioavailability Biotechnology Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Breast Neoplasms - microbiology Breast Neoplasms - pathology Cell Line, Tumor Cellular structure Conjugation Controlled release Curcumin Curcumin - chemistry Curcumin - pharmacology Cytotoxicity Drug Carriers - chemistry Drug Carriers - pharmacology Drug delivery Drug delivery systems E coli Escherichia coli - growth & development Escherichia coli Infections - drug therapy Escherichia coli Infections - metabolism Escherichia coli Infections - pathology Female Folic acid Folic Acid - pharmacology Folic acid receptor targeting Functional groups HEK293 Cells Humans Hydrophobicity Materials science Mathematical models Minimum inhibitory concentration Nanostructure Nanostructures - chemistry Nanostructures - therapeutic use Non-spherical drug delivery systems Staphylococcal Infections - drug therapy Staphylococcal Infections - metabolism Staphylococcal Infections - pathology Staphylococcus aureus - growth & development Sustained release Zinc Zinc oxide Zinc Oxide - chemistry Zinc Oxide - pharmacology Zinc oxide nanostructures Zinc oxides |
| title | Flower-like curcumin-loaded folic acid-conjugated ZnO-MPA- βcyclodextrin nanostructures enhanced anticancer activity and cellular uptake of curcumin in breast cancer cells |
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