Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies
Homodimeric prodrug-based self-assembled nanoparticles, with carrier-free structure and ultrahigh drug loading, is drawing more and more attentions. Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage. The influence of the linkages on the self-assembly, in vivo fate and ant...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-05-01
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| Series: | Asian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087621000155 |
| _version_ | 1818886475107794944 |
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| author | Lingxiao Li Shiyi Zuo Fudan Dong Tian Liu Yanlin Gao Yinxian Yang Xin Wang Jin Sun Bingjun Sun Zhonggui He |
| author_facet | Lingxiao Li Shiyi Zuo Fudan Dong Tian Liu Yanlin Gao Yinxian Yang Xin Wang Jin Sun Bingjun Sun Zhonggui He |
| author_sort | Lingxiao Li |
| collection | DOAJ |
| description | Homodimeric prodrug-based self-assembled nanoparticles, with carrier-free structure and ultrahigh drug loading, is drawing more and more attentions. Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage. The influence of the linkages on the self-assembly, in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research. Herein, three docetaxel (DTX) homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages. Interestingly, compared with the other two linkages, the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs, thus improving the stability, circulation time and tumor targeting of prodrug nanoassemblies. Besides, the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells. Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells, their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells, which finally “turned the table”. Our study illustrates the crucial role of linkages in homodimeric prodrugs, and gives valuable proposal for the development of advanced nano-DDS for cancer treatment. |
| first_indexed | 2024-12-19T16:21:55Z |
| format | Article |
| id | doaj.art-1d4cafde6b31468cacf79f4fb432bcd4 |
| institution | Directory Open Access Journal |
| issn | 1818-0876 |
| language | English |
| last_indexed | 2024-12-19T16:21:55Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-1d4cafde6b31468cacf79f4fb432bcd42022-12-21T20:14:27ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762021-05-01163337349Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassembliesLingxiao Li0Shiyi Zuo1Fudan Dong2Tian Liu3Yanlin Gao4Yinxian Yang5Xin Wang6Jin Sun7Bingjun Sun8Zhonggui He9Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaCorresponding authors.; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaCorresponding authors.; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaHomodimeric prodrug-based self-assembled nanoparticles, with carrier-free structure and ultrahigh drug loading, is drawing more and more attentions. Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage. The influence of the linkages on the self-assembly, in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research. Herein, three docetaxel (DTX) homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages. Interestingly, compared with the other two linkages, the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs, thus improving the stability, circulation time and tumor targeting of prodrug nanoassemblies. Besides, the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells. Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells, their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells, which finally “turned the table”. Our study illustrates the crucial role of linkages in homodimeric prodrugs, and gives valuable proposal for the development of advanced nano-DDS for cancer treatment.http://www.sciencedirect.com/science/article/pii/S1818087621000155Diselenide bondHomodimeric prodrugDocetaxelSelf-assemblyRedox responsive |
| spellingShingle | Lingxiao Li Shiyi Zuo Fudan Dong Tian Liu Yanlin Gao Yinxian Yang Xin Wang Jin Sun Bingjun Sun Zhonggui He Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies Asian Journal of Pharmaceutical Sciences Diselenide bond Homodimeric prodrug Docetaxel Self-assembly Redox responsive |
| title | Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies |
| title_full | Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies |
| title_fullStr | Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies |
| title_full_unstemmed | Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies |
| title_short | Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies |
| title_sort | small changes in the length of diselenide bond containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies |
| topic | Diselenide bond Homodimeric prodrug Docetaxel Self-assembly Redox responsive |
| url | http://www.sciencedirect.com/science/article/pii/S1818087621000155 |
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