Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug
Curcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), di...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Carbohydrate Polymer Technologies and Applications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666893923000452 |
| _version_ | 1797801662688002048 |
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| author | Zi-Dan Wang Hu-Hong Peng Dong-Qiang Lin Yi-Xin Guan |
| author_facet | Zi-Dan Wang Hu-Hong Peng Dong-Qiang Lin Yi-Xin Guan |
| author_sort | Zi-Dan Wang |
| collection | DOAJ |
| description | Curcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), disulfide bond (QHES-SS-CUR), and carbon-carbon bond (QHES-CC-CUR) were implemented, respectively. The effect of above three linkers on the self-assembly behavior of QHES-curcumin prodrugs was evaluated. QHES-2S-CUR and QHES-SS-CUR could facilely self-assemble into spherical micelles in water, while QHES-CC-CUR was lack of conformational stability. In vitro drug release profiles of prodrug micelles were further investigated. Concretely, QHES-2S-CUR presented ROS-sensitive drug release, with 73.57 ± 4.22% of curcumin released under the addition of H2O2 over 24 h. The release of curcumin from QHES-SS-CUR lasted for 54 h due to the slower oxidization of disulfide bonds, and QHES-CC-CUR was insensitive to ROS. In addition, QHES-2S-CUR prodrug micelles demonstrated superior cytotoxicity to murine colonic adenocarcinoma (CT-26) cells compared to QHES-SS-CUR and QHES-CC-CUR, which were internalized by CT-26 cells with high efficiency. These results reveal the potential of QHES-2S-CUR prodrug micelles as tumor microenvironment-responsive anticarcinogen. |
| first_indexed | 2024-03-13T04:54:57Z |
| format | Article |
| id | doaj.art-c6d2623841614c9eb37afd2dea2c3d6f |
| institution | Directory Open Access Journal |
| issn | 2666-8939 |
| language | English |
| last_indexed | 2024-03-13T04:54:57Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Carbohydrate Polymer Technologies and Applications |
| spelling | doaj.art-c6d2623841614c9eb37afd2dea2c3d6f2023-06-18T05:03:50ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392023-06-015100324Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrugZi-Dan Wang0Hu-Hong Peng1Dong-Qiang Lin2Yi-Xin Guan3Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, ChinaZhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, ChinaZhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, ChinaCorresponding author.; Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, ChinaCurcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), disulfide bond (QHES-SS-CUR), and carbon-carbon bond (QHES-CC-CUR) were implemented, respectively. The effect of above three linkers on the self-assembly behavior of QHES-curcumin prodrugs was evaluated. QHES-2S-CUR and QHES-SS-CUR could facilely self-assemble into spherical micelles in water, while QHES-CC-CUR was lack of conformational stability. In vitro drug release profiles of prodrug micelles were further investigated. Concretely, QHES-2S-CUR presented ROS-sensitive drug release, with 73.57 ± 4.22% of curcumin released under the addition of H2O2 over 24 h. The release of curcumin from QHES-SS-CUR lasted for 54 h due to the slower oxidization of disulfide bonds, and QHES-CC-CUR was insensitive to ROS. In addition, QHES-2S-CUR prodrug micelles demonstrated superior cytotoxicity to murine colonic adenocarcinoma (CT-26) cells compared to QHES-SS-CUR and QHES-CC-CUR, which were internalized by CT-26 cells with high efficiency. These results reveal the potential of QHES-2S-CUR prodrug micelles as tumor microenvironment-responsive anticarcinogen.http://www.sciencedirect.com/science/article/pii/S2666893923000452Hydroxyethyl starchCurcuminProdrugLinkerROS-responsiveSelf-assembly |
| spellingShingle | Zi-Dan Wang Hu-Hong Peng Dong-Qiang Lin Yi-Xin Guan Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug Carbohydrate Polymer Technologies and Applications Hydroxyethyl starch Curcumin Prodrug Linker ROS-responsive Self-assembly |
| title | Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug |
| title_full | Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug |
| title_fullStr | Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug |
| title_full_unstemmed | Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug |
| title_short | Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug |
| title_sort | exploring the effect of different linkers on self assembly ros sensitivity and anticancer efficacy of hydroxyethyl starch curcumin prodrug |
| topic | Hydroxyethyl starch Curcumin Prodrug Linker ROS-responsive Self-assembly |
| url | http://www.sciencedirect.com/science/article/pii/S2666893923000452 |
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