Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer
Cabazitaxel (CTX) is a medication used for treating metastatic prostate cancer. However, its effectiveness is majorly limited by its poor water solubility and lack of tumor targeting. In this study, three unsaturated fatty acids, GLA, ALA and DHA, were separately connected with CTX and then covalent...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223017006 |
| _version_ | 1797404555980308480 |
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| author | Hongshuai Lv Weiping Jia Li Yang Peng Dong Jiaojiao Liu Si Wang Xiaohai Li Jinghua Hu Ling Zhao Yikang Shi |
| author_facet | Hongshuai Lv Weiping Jia Li Yang Peng Dong Jiaojiao Liu Si Wang Xiaohai Li Jinghua Hu Ling Zhao Yikang Shi |
| author_sort | Hongshuai Lv |
| collection | DOAJ |
| description | Cabazitaxel (CTX) is a medication used for treating metastatic prostate cancer. However, its effectiveness is majorly limited by its poor water solubility and lack of tumor targeting. In this study, three unsaturated fatty acids, GLA, ALA and DHA, were separately connected with CTX and then covalently attached to bifunctionalized dextran through a linker to produce three dual drug conjugates named dextran-GLA-CTX, dextran-ALA-CTX and dextran-DHA-CTX. The three conjugates displayed enhanced solubility of CTX in water and improved antitumor effects compared to the conventional CTX formulation. The results also confirmed that dextran-GLA-CTX exhibited the strongest antitumor activity, while dextran-DHA-CTX displayed less efficacy, as evaluated through xenografted nude mice bearing PC-3 and DU145 prostate cancer cells. Additionally, dextran-GLA-CTX showed greater inhibition of tumor growth than dextran-CTX. Moreover, the dextran-GLA-CTX conjugate was found to prolong the half-life of CTX in plasma and selectively accumulate in tumors. This study revealed that unsaturated fatty acids can enhance the antitumor activity of dextran-based conjugates grafted with CTX. |
| first_indexed | 2024-03-09T02:56:43Z |
| format | Article |
| id | doaj.art-0f59cccaec0e4fd688dc12fd100e8af0 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-09T02:56:43Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-0f59cccaec0e4fd688dc12fd100e8af02023-12-05T04:14:44ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01169115902Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancerHongshuai Lv0Weiping Jia1Li Yang2Peng Dong3Jiaojiao Liu4Si Wang5Xiaohai Li6Jinghua Hu7Ling Zhao8Yikang Shi9National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based Medicine, Shandong University, Qingdao, Shandong, 266237, PR ChinaNational Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based Medicine, Shandong University, Qingdao, Shandong, 266237, PR ChinaNational Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based Medicine, Shandong University, Qingdao, Shandong, 266237, PR ChinaNational Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based Medicine, Shandong University, Qingdao, Shandong, 266237, PR ChinaNational Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based Medicine, Shandong University, Qingdao, Shandong, 266237, PR ChinaSantolecan Pharmaceuticals LLC, Jupiter, Florida 33458, United StatesSantolecan Pharmaceuticals LLC, Jupiter, Florida 33458, United StatesSantolecan Pharmaceuticals LLC, Jupiter, Florida 33458, United StatesSantolecan Pharmaceuticals LLC, Jupiter, Florida 33458, United StatesNational Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based Medicine, Shandong University, Qingdao, Shandong, 266237, PR China; Corresponding author.Cabazitaxel (CTX) is a medication used for treating metastatic prostate cancer. However, its effectiveness is majorly limited by its poor water solubility and lack of tumor targeting. In this study, three unsaturated fatty acids, GLA, ALA and DHA, were separately connected with CTX and then covalently attached to bifunctionalized dextran through a linker to produce three dual drug conjugates named dextran-GLA-CTX, dextran-ALA-CTX and dextran-DHA-CTX. The three conjugates displayed enhanced solubility of CTX in water and improved antitumor effects compared to the conventional CTX formulation. The results also confirmed that dextran-GLA-CTX exhibited the strongest antitumor activity, while dextran-DHA-CTX displayed less efficacy, as evaluated through xenografted nude mice bearing PC-3 and DU145 prostate cancer cells. Additionally, dextran-GLA-CTX showed greater inhibition of tumor growth than dextran-CTX. Moreover, the dextran-GLA-CTX conjugate was found to prolong the half-life of CTX in plasma and selectively accumulate in tumors. This study revealed that unsaturated fatty acids can enhance the antitumor activity of dextran-based conjugates grafted with CTX.http://www.sciencedirect.com/science/article/pii/S0753332223017006CabazitaxelDextranConjugateAlpha-linolenic acidGamma-linolenic acidDocosahexaenoic acid |
| spellingShingle | Hongshuai Lv Weiping Jia Li Yang Peng Dong Jiaojiao Liu Si Wang Xiaohai Li Jinghua Hu Ling Zhao Yikang Shi Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer Biomedicine & Pharmacotherapy Cabazitaxel Dextran Conjugate Alpha-linolenic acid Gamma-linolenic acid Docosahexaenoic acid |
| title | Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer |
| title_full | Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer |
| title_fullStr | Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer |
| title_full_unstemmed | Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer |
| title_short | Influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer |
| title_sort | influence of unsaturated fatty acids on the antitumor activity of polymeric conjugates grafted with cabazitaxel against prostate cancer |
| topic | Cabazitaxel Dextran Conjugate Alpha-linolenic acid Gamma-linolenic acid Docosahexaenoic acid |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223017006 |
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