Biotin-Modified Polylactic-co-Glycolic Acid Nanoparticles with Improved Antiproliferative Activity of 15,16-Dihydrotanshinone I in Human Cervical Cancer Cells
15,16-Dihydrotanshinone I (DI), a natural compound isolated from a traditional Asian functional food Salvia Miltiorrhiza Bunge, is known for its anticancer activity. However, poor solubility of DI limits its desirable anticancer application. Herein, polylactic-co-glycolic acid (PLGA) was functionali...
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| Veröffentlicht in: | Journal of agricultural and food chemistry 2018-09, Vol.66 (35), p.9219-9230 |
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| container_title | Journal of agricultural and food chemistry |
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| creator | Luo, Jingjing Meng, Xiaofeng Su, Jianyu Ma, Hang Wang, Wen Fang, Liming Zheng, Huade Qin, Yexia Chen, Tianfeng |
| description | 15,16-Dihydrotanshinone I (DI), a natural compound isolated from a traditional Asian functional food Salvia Miltiorrhiza Bunge, is known for its anticancer activity. However, poor solubility of DI limits its desirable anticancer application. Herein, polylactic-co-glycolic acid (PLGA) was functionalized with polyethylene glycol (PEG) and biotin to form copolymers PEG-PLGA (PPA) and biotin-PEG-PLGA (BPA). DI was encapsulated in copolymers PPA and BPA to obtain DI-PPA-NPs (NPs = nanoparticles) and DI-BPA-NPs, respectively. The particle size and its distribution, encapsulation efficiency, and in vitro releasing capacity of DI-BPA-NPs were characterized by biophysical methods. MTT assay was used to evaluate the antiproliferative activity of free DI, DI-PPA-NPs, and DI-BPA-NPs in human cervical cancer Hela cells. DI-BPA-NPs showed the highest cytotoxicity on Hela cells with an IC50 value of 4.55 ± 0.631 μM, while it was 8.20 ± 0.849 and 6.14 ± 0.312 μM for DI and DI-PPA-NPs in 72 h, respectively. The superior antiproliferative activity was supported by the fact that DI-BPA-NPs could be preferentially internalized by Hela cells, owing to their specific interaction between biotin and overexpressed biotin receptors. In addition, DI-BPA-NPs effectively inhibited Hela cell proliferation by inducing G2/M phase cycle arrest and decreasing the intracellular reactive oxygen species (ROS) level by 31.50 ± 2.29% in 5 min. In summary, DI-BPA-NPs shows improved antiproliferative activity against human cervical cancer as comparing with free DI, demonstrating its application potential in cancer therapy. |
| doi_str_mv | 10.1021/acs.jafc.8b02698 |
| format | Article |
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However, poor solubility of DI limits its desirable anticancer application. Herein, polylactic-co-glycolic acid (PLGA) was functionalized with polyethylene glycol (PEG) and biotin to form copolymers PEG-PLGA (PPA) and biotin-PEG-PLGA (BPA). DI was encapsulated in copolymers PPA and BPA to obtain DI-PPA-NPs (NPs = nanoparticles) and DI-BPA-NPs, respectively. The particle size and its distribution, encapsulation efficiency, and in vitro releasing capacity of DI-BPA-NPs were characterized by biophysical methods. MTT assay was used to evaluate the antiproliferative activity of free DI, DI-PPA-NPs, and DI-BPA-NPs in human cervical cancer Hela cells. DI-BPA-NPs showed the highest cytotoxicity on Hela cells with an IC50 value of 4.55 ± 0.631 μM, while it was 8.20 ± 0.849 and 6.14 ± 0.312 μM for DI and DI-PPA-NPs in 72 h, respectively. The superior antiproliferative activity was supported by the fact that DI-BPA-NPs could be preferentially internalized by Hela cells, owing to their specific interaction between biotin and overexpressed biotin receptors. In addition, DI-BPA-NPs effectively inhibited Hela cell proliferation by inducing G2/M phase cycle arrest and decreasing the intracellular reactive oxygen species (ROS) level by 31.50 ± 2.29% in 5 min. In summary, DI-BPA-NPs shows improved antiproliferative activity against human cervical cancer as comparing with free DI, demonstrating its application potential in cancer therapy.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/acs.jafc.8b02698</identifier><identifier>PMID: 30102527</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Biotin - chemistry ; Cell Cycle - drug effects ; Cell Proliferation - drug effects ; Drug Carriers - chemical synthesis ; Drug Carriers - chemistry ; Drug Compounding ; Drug Delivery Systems ; Drugs, Chinese Herbal - chemistry ; Drugs, Chinese Herbal - pharmacology ; Female ; Glycolates - chemistry ; HeLa Cells ; Humans ; Particle Size ; Phenanthrenes - chemistry ; Phenanthrenes - pharmacology ; Polyesters - chemistry ; Reactive Oxygen Species - metabolism ; Salvia miltiorrhiza - chemistry ; Uterine Cervical Neoplasms - drug therapy ; Uterine Cervical Neoplasms - metabolism ; Uterine Cervical Neoplasms - physiopathology</subject><ispartof>Journal of agricultural and food chemistry, 2018-09, Vol.66 (35), p.9219-9230</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a336t-b3ab5f1ce204abd1a7fc89aa9800105331f9712d0068f1cff46bc33619cc7c73</citedby><cites>FETCH-LOGICAL-a336t-b3ab5f1ce204abd1a7fc89aa9800105331f9712d0068f1cff46bc33619cc7c73</cites><orcidid>0000-0001-6953-1342 ; 0000-0001-7565-6889 ; 0000-0002-1662-0461</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jafc.8b02698$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jafc.8b02698$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30102527$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Jingjing</creatorcontrib><creatorcontrib>Meng, Xiaofeng</creatorcontrib><creatorcontrib>Su, Jianyu</creatorcontrib><creatorcontrib>Ma, Hang</creatorcontrib><creatorcontrib>Wang, Wen</creatorcontrib><creatorcontrib>Fang, Liming</creatorcontrib><creatorcontrib>Zheng, Huade</creatorcontrib><creatorcontrib>Qin, Yexia</creatorcontrib><creatorcontrib>Chen, Tianfeng</creatorcontrib><title>Biotin-Modified Polylactic-co-Glycolic Acid Nanoparticles with Improved Antiproliferative Activity of 15,16-Dihydrotanshinone I in Human Cervical Cancer Cells</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>15,16-Dihydrotanshinone I (DI), a natural compound isolated from a traditional Asian functional food Salvia Miltiorrhiza Bunge, is known for its anticancer activity. However, poor solubility of DI limits its desirable anticancer application. Herein, polylactic-co-glycolic acid (PLGA) was functionalized with polyethylene glycol (PEG) and biotin to form copolymers PEG-PLGA (PPA) and biotin-PEG-PLGA (BPA). DI was encapsulated in copolymers PPA and BPA to obtain DI-PPA-NPs (NPs = nanoparticles) and DI-BPA-NPs, respectively. The particle size and its distribution, encapsulation efficiency, and in vitro releasing capacity of DI-BPA-NPs were characterized by biophysical methods. MTT assay was used to evaluate the antiproliferative activity of free DI, DI-PPA-NPs, and DI-BPA-NPs in human cervical cancer Hela cells. DI-BPA-NPs showed the highest cytotoxicity on Hela cells with an IC50 value of 4.55 ± 0.631 μM, while it was 8.20 ± 0.849 and 6.14 ± 0.312 μM for DI and DI-PPA-NPs in 72 h, respectively. The superior antiproliferative activity was supported by the fact that DI-BPA-NPs could be preferentially internalized by Hela cells, owing to their specific interaction between biotin and overexpressed biotin receptors. In addition, DI-BPA-NPs effectively inhibited Hela cell proliferation by inducing G2/M phase cycle arrest and decreasing the intracellular reactive oxygen species (ROS) level by 31.50 ± 2.29% in 5 min. In summary, DI-BPA-NPs shows improved antiproliferative activity against human cervical cancer as comparing with free DI, demonstrating its application potential in cancer therapy.</description><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biotin - chemistry</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Drug Carriers - chemical synthesis</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Compounding</subject><subject>Drug Delivery Systems</subject><subject>Drugs, Chinese Herbal - chemistry</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Female</subject><subject>Glycolates - chemistry</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Particle Size</subject><subject>Phenanthrenes - chemistry</subject><subject>Phenanthrenes - pharmacology</subject><subject>Polyesters - chemistry</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Salvia miltiorrhiza - chemistry</subject><subject>Uterine Cervical Neoplasms - drug therapy</subject><subject>Uterine Cervical Neoplasms - metabolism</subject><subject>Uterine Cervical Neoplasms - physiopathology</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1v1DAQhi0Eokvhzgn5yKFZxkmTOMdlgXal8nHoPZpMbK0rx15sZ6v8GX4rLrtw4zS2_Dwjv3oZeytgLaAUH5Di-gE1reUAZdPJZ2wl6hKKWgj5nK0gM4WsG3HBXsX4AACybuElu6gg63XZrtivj8Yn44qvfjTaqJH_8HaxSMlQQb64sQt5a4hvyIz8Gzp_wJDfrIr80aQ9302H4I_Z27hk8tEarQImc1RZycOkhXvNRX0lmuKT2S9j8Ald3BvnneI7bhy_nSd0fKvC0RBavkVHKuS7tfE1e6HRRvXmPC_Z_ZfP99vb4u77zW67uSuwqppUDBUOtRakSrjGYRTYapIdYichJ62rSuiuFeUI0MiMaX3dDJRN0RG11FaX7P1pbU7wc1Yx9ZOJlD-ATvk59iVIWXbQVJBROKEUfIxB6f4QzIRh6QX0T6X0uZT-qZT-XEpW3p23z8Okxn_C3xYycHUC_qh-Di5n_f--34zFmn4</recordid><startdate>20180905</startdate><enddate>20180905</enddate><creator>Luo, Jingjing</creator><creator>Meng, Xiaofeng</creator><creator>Su, Jianyu</creator><creator>Ma, Hang</creator><creator>Wang, Wen</creator><creator>Fang, Liming</creator><creator>Zheng, Huade</creator><creator>Qin, Yexia</creator><creator>Chen, Tianfeng</creator><general>American Chemical Society</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>7X8</scope><orcidid>https://orcid.org/0000-0001-6953-1342</orcidid><orcidid>https://orcid.org/0000-0001-7565-6889</orcidid><orcidid>https://orcid.org/0000-0002-1662-0461</orcidid></search><sort><creationdate>20180905</creationdate><title>Biotin-Modified Polylactic-co-Glycolic Acid Nanoparticles with Improved Antiproliferative Activity of 15,16-Dihydrotanshinone I in Human Cervical Cancer Cells</title><author>Luo, Jingjing ; Meng, Xiaofeng ; Su, Jianyu ; Ma, Hang ; Wang, Wen ; Fang, Liming ; Zheng, Huade ; Qin, Yexia ; Chen, Tianfeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a336t-b3ab5f1ce204abd1a7fc89aa9800105331f9712d0068f1cff46bc33619cc7c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biotin - chemistry</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Drug Carriers - chemical synthesis</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Compounding</topic><topic>Drug Delivery Systems</topic><topic>Drugs, Chinese Herbal - chemistry</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Female</topic><topic>Glycolates - chemistry</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Particle Size</topic><topic>Phenanthrenes - chemistry</topic><topic>Phenanthrenes - pharmacology</topic><topic>Polyesters - chemistry</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Salvia miltiorrhiza - chemistry</topic><topic>Uterine Cervical Neoplasms - drug therapy</topic><topic>Uterine Cervical Neoplasms - metabolism</topic><topic>Uterine Cervical Neoplasms - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Jingjing</creatorcontrib><creatorcontrib>Meng, Xiaofeng</creatorcontrib><creatorcontrib>Su, Jianyu</creatorcontrib><creatorcontrib>Ma, Hang</creatorcontrib><creatorcontrib>Wang, Wen</creatorcontrib><creatorcontrib>Fang, Liming</creatorcontrib><creatorcontrib>Zheng, Huade</creatorcontrib><creatorcontrib>Qin, Yexia</creatorcontrib><creatorcontrib>Chen, Tianfeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Jingjing</au><au>Meng, Xiaofeng</au><au>Su, Jianyu</au><au>Ma, Hang</au><au>Wang, Wen</au><au>Fang, Liming</au><au>Zheng, Huade</au><au>Qin, Yexia</au><au>Chen, Tianfeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biotin-Modified Polylactic-co-Glycolic Acid Nanoparticles with Improved Antiproliferative Activity of 15,16-Dihydrotanshinone I in Human Cervical Cancer Cells</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2018-09-05</date><risdate>2018</risdate><volume>66</volume><issue>35</issue><spage>9219</spage><epage>9230</epage><pages>9219-9230</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><abstract>15,16-Dihydrotanshinone I (DI), a natural compound isolated from a traditional Asian functional food Salvia Miltiorrhiza Bunge, is known for its anticancer activity. However, poor solubility of DI limits its desirable anticancer application. Herein, polylactic-co-glycolic acid (PLGA) was functionalized with polyethylene glycol (PEG) and biotin to form copolymers PEG-PLGA (PPA) and biotin-PEG-PLGA (BPA). DI was encapsulated in copolymers PPA and BPA to obtain DI-PPA-NPs (NPs = nanoparticles) and DI-BPA-NPs, respectively. The particle size and its distribution, encapsulation efficiency, and in vitro releasing capacity of DI-BPA-NPs were characterized by biophysical methods. MTT assay was used to evaluate the antiproliferative activity of free DI, DI-PPA-NPs, and DI-BPA-NPs in human cervical cancer Hela cells. DI-BPA-NPs showed the highest cytotoxicity on Hela cells with an IC50 value of 4.55 ± 0.631 μM, while it was 8.20 ± 0.849 and 6.14 ± 0.312 μM for DI and DI-PPA-NPs in 72 h, respectively. The superior antiproliferative activity was supported by the fact that DI-BPA-NPs could be preferentially internalized by Hela cells, owing to their specific interaction between biotin and overexpressed biotin receptors. In addition, DI-BPA-NPs effectively inhibited Hela cell proliferation by inducing G2/M phase cycle arrest and decreasing the intracellular reactive oxygen species (ROS) level by 31.50 ± 2.29% in 5 min. In summary, DI-BPA-NPs shows improved antiproliferative activity against human cervical cancer as comparing with free DI, demonstrating its application potential in cancer therapy.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>30102527</pmid><doi>10.1021/acs.jafc.8b02698</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-6953-1342</orcidid><orcidid>https://orcid.org/0000-0001-7565-6889</orcidid><orcidid>https://orcid.org/0000-0002-1662-0461</orcidid></addata></record> |
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| subjects | Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biotin - chemistry Cell Cycle - drug effects Cell Proliferation - drug effects Drug Carriers - chemical synthesis Drug Carriers - chemistry Drug Compounding Drug Delivery Systems Drugs, Chinese Herbal - chemistry Drugs, Chinese Herbal - pharmacology Female Glycolates - chemistry HeLa Cells Humans Particle Size Phenanthrenes - chemistry Phenanthrenes - pharmacology Polyesters - chemistry Reactive Oxygen Species - metabolism Salvia miltiorrhiza - chemistry Uterine Cervical Neoplasms - drug therapy Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - physiopathology |
| title | Biotin-Modified Polylactic-co-Glycolic Acid Nanoparticles with Improved Antiproliferative Activity of 15,16-Dihydrotanshinone I in Human Cervical Cancer Cells |
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