Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer
Endostatin (ES) can effectively inhibit neovascularization in most solid tumors and has the potential to make oxygen delivery more efficient and increase the efficacy of radiotherapy (RT). With a short half-life, ES is mainly administered systemically, which leads to low intake in tumor tissue and o...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10717544.2020.1869864 |
| _version_ | 1818987168258850816 |
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| author | Na Wang Qin Gao Juan Tang YiQing Jiang LiShi Yang XiangXiang Shi Yue Chen Yan Zhang ShaoZhi Fu Sheng Lin |
| author_facet | Na Wang Qin Gao Juan Tang YiQing Jiang LiShi Yang XiangXiang Shi Yue Chen Yan Zhang ShaoZhi Fu Sheng Lin |
| author_sort | Na Wang |
| collection | DOAJ |
| description | Endostatin (ES) can effectively inhibit neovascularization in most solid tumors and has the potential to make oxygen delivery more efficient and increase the efficacy of radiotherapy (RT). With a short half-life, ES is mainly administered systemically, which leads to low intake in tumor tissue and often toxic systemic side effects. In this study, we used hyaluronic acid-tyramine as a carrier to synthesize an ES-loaded hydrogel drug (ES/HA-Tyr) that can be injected locally. ES/HA-Tyr has a longer half-life and fewer systemic toxic side effects, and it exerts a better anti-angiogenic effect and anti-tumor effect with RT. In vitro, ES/HA-Tyr showed sustained release in the release assay and a stronger ability to inhibit the proliferation of human umbilical vascular endothelial cells (HUVECs) in the MTT assay; it exhibited a more potent effect against HUVEC invasion and a stronger anti-angiogenic effect on HUVECs in tube formation. In vivo, ES/HA-Tyr increased local drug concentration, decreased blood drug concentration, and caused less systemic toxicity. Further, ES/HA-Tyr effectively reduced tumor microvessel density, increased tumor pericyte coverage, decreased tumor hypoxia, and increased RT response. ES/HA-Tyr + RT also had increased anti-tumor and anti-angiogenic effects in Lewis lung cancer (LLC) xenograft models. In conclusion, ES/HA-Tyr showed sustained release, lower systemic toxicity, and better anti-tumor effects than ES. In addition, ES/HA-Tyr + RT enhanced anti-angiogenic effects, reduced tumor hypoxia, and increased the efficacy of RT in LLC-bearing mice. |
| first_indexed | 2024-12-20T19:02:24Z |
| format | Article |
| id | doaj.art-56fcdda9f146420faddc4ab8fa455cf9 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-20T19:02:24Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-56fcdda9f146420faddc4ab8fa455cf92022-12-21T19:29:22ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642021-01-0128118319410.1080/10717544.2020.18698641869864Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancerNa Wang0Qin Gao1Juan Tang2YiQing Jiang3LiShi Yang4XiangXiang Shi5Yue Chen6Yan Zhang7ShaoZhi Fu8Sheng Lin9Department of Oncology, Affiliated Hospital of Southwest Medical UniversityDepartment of Oncology, Affiliated Hospital of Southwest Medical UniversityDepartment of Oncology, Affiliated Hospital of Southwest Medical UniversityDepartment of Oncology, Affiliated Hospital of Southwest Medical UniversityDepartment of Oncology, Affiliated Hospital of Southwest Medical UniversityDepartment of Oncology, Affiliated Hospital of Southwest Medical UniversityNuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical UniversityNuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical UniversityDepartment of Oncology, Affiliated Hospital of Southwest Medical UniversityDepartment of Oncology, Affiliated Hospital of Southwest Medical UniversityEndostatin (ES) can effectively inhibit neovascularization in most solid tumors and has the potential to make oxygen delivery more efficient and increase the efficacy of radiotherapy (RT). With a short half-life, ES is mainly administered systemically, which leads to low intake in tumor tissue and often toxic systemic side effects. In this study, we used hyaluronic acid-tyramine as a carrier to synthesize an ES-loaded hydrogel drug (ES/HA-Tyr) that can be injected locally. ES/HA-Tyr has a longer half-life and fewer systemic toxic side effects, and it exerts a better anti-angiogenic effect and anti-tumor effect with RT. In vitro, ES/HA-Tyr showed sustained release in the release assay and a stronger ability to inhibit the proliferation of human umbilical vascular endothelial cells (HUVECs) in the MTT assay; it exhibited a more potent effect against HUVEC invasion and a stronger anti-angiogenic effect on HUVECs in tube formation. In vivo, ES/HA-Tyr increased local drug concentration, decreased blood drug concentration, and caused less systemic toxicity. Further, ES/HA-Tyr effectively reduced tumor microvessel density, increased tumor pericyte coverage, decreased tumor hypoxia, and increased RT response. ES/HA-Tyr + RT also had increased anti-tumor and anti-angiogenic effects in Lewis lung cancer (LLC) xenograft models. In conclusion, ES/HA-Tyr showed sustained release, lower systemic toxicity, and better anti-tumor effects than ES. In addition, ES/HA-Tyr + RT enhanced anti-angiogenic effects, reduced tumor hypoxia, and increased the efficacy of RT in LLC-bearing mice.http://dx.doi.org/10.1080/10717544.2020.1869864endostatinhyaluronic acidhydrogelradiotherapylung cancer |
| spellingShingle | Na Wang Qin Gao Juan Tang YiQing Jiang LiShi Yang XiangXiang Shi Yue Chen Yan Zhang ShaoZhi Fu Sheng Lin Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer Drug Delivery endostatin hyaluronic acid hydrogel radiotherapy lung cancer |
| title | Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer |
| title_full | Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer |
| title_fullStr | Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer |
| title_full_unstemmed | Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer |
| title_short | Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer |
| title_sort | anti tumor effect of local injectable hydrogel loaded endostatin alone and in combination with radiotherapy for lung cancer |
| topic | endostatin hyaluronic acid hydrogel radiotherapy lung cancer |
| url | http://dx.doi.org/10.1080/10717544.2020.1869864 |
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