Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive Nanoparticles
The serious therapeutic obstacles to glioma treatment include poor penetration across the blood-brain barrier (BBB) and low accumulation of therapeutic drugs at tumor sites. In this study, borneol combined with CGKRK peptide (a ligand of the heparan sulfate which overexpress on the glioma cells) mod...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00558/full |
| _version_ | 1818897628141715456 |
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| author | Lingyan Lv Lingyan Lv Xinrui Li Xinrui Li Wei Qian Shennan Li Yan Jiang Yaokun Xiong Jianpei Xu Wei Lv Xiaoyan Liu Yun Chen Yulin Tang Hongliang Xin |
| author_facet | Lingyan Lv Lingyan Lv Xinrui Li Xinrui Li Wei Qian Shennan Li Yan Jiang Yaokun Xiong Jianpei Xu Wei Lv Xiaoyan Liu Yun Chen Yulin Tang Hongliang Xin |
| author_sort | Lingyan Lv |
| collection | DOAJ |
| description | The serious therapeutic obstacles to glioma treatment include poor penetration across the blood-brain barrier (BBB) and low accumulation of therapeutic drugs at tumor sites. In this study, borneol combined with CGKRK peptide (a ligand of the heparan sulfate which overexpress on the glioma cells) modified paclitaxel prodrug self-assembled redox-responsive nanoparticles (CGKRK-PSNPs) were hypothesized to enhance the BBB penetration ability and active tumor targeting efficiency, respectively. The resulting CGKRK-PSNPs possessed a spherical shape with a small particle size (105.61 ± 1.53 nm) and high drug loading for PTX (54.18 ± 1.13%). The drug release behavior proved that CGKRK-PSNPs were highly sensitive to glutathione (GSH) redox environment. The in vitro cell experiments suggested that CGKRK-PSNPs significantly increased the cellular uptake and cytotoxicity of U87MG cells, meanwhile CGKRK-PSNPs showed the low cytotoxicity against BCEC cells. Combined with borneol, CGKRK-PSNPs exhibited enhanced transportation across in vitro BBB model. In intracranial U87MG glioma-bearing nude mice, the higher accumulation of CGKRK-PSNPs combined with borneol was observed through real-time fluorescence image. Moreover, the in vivo anti-glioma results confirmed that CGKRK-PSNPs combined with borneol could improve the anti-glioma efficacy with the prolonged medium survival time (39 days). In conclusion, the collaborative strategy of CGKRK-PSNPs combined with borneol provided a promising drug delivery routine for glioblastoma therapy. |
| first_indexed | 2024-12-19T19:19:12Z |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T19:19:12Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-7fa9ad9d0ac34d2fb2cb3c67d902f3432022-12-21T20:09:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-04-011110.3389/fphar.2020.00558539205Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive NanoparticlesLingyan Lv0Lingyan Lv1Xinrui Li2Xinrui Li3Wei Qian4Shennan Li5Yan Jiang6Yaokun Xiong7Jianpei Xu8Wei Lv9Xiaoyan Liu10Yun Chen11Yulin Tang12Hongliang Xin13Department of Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacy, Zhangjiagang Hospital of Traditional Chinese Medicine, Affiliated Nanjing University of Chinese Medicine, Zhangjiagang, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, ChinaSchool of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, ChinaDepartment of Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, ChinaThe serious therapeutic obstacles to glioma treatment include poor penetration across the blood-brain barrier (BBB) and low accumulation of therapeutic drugs at tumor sites. In this study, borneol combined with CGKRK peptide (a ligand of the heparan sulfate which overexpress on the glioma cells) modified paclitaxel prodrug self-assembled redox-responsive nanoparticles (CGKRK-PSNPs) were hypothesized to enhance the BBB penetration ability and active tumor targeting efficiency, respectively. The resulting CGKRK-PSNPs possessed a spherical shape with a small particle size (105.61 ± 1.53 nm) and high drug loading for PTX (54.18 ± 1.13%). The drug release behavior proved that CGKRK-PSNPs were highly sensitive to glutathione (GSH) redox environment. The in vitro cell experiments suggested that CGKRK-PSNPs significantly increased the cellular uptake and cytotoxicity of U87MG cells, meanwhile CGKRK-PSNPs showed the low cytotoxicity against BCEC cells. Combined with borneol, CGKRK-PSNPs exhibited enhanced transportation across in vitro BBB model. In intracranial U87MG glioma-bearing nude mice, the higher accumulation of CGKRK-PSNPs combined with borneol was observed through real-time fluorescence image. Moreover, the in vivo anti-glioma results confirmed that CGKRK-PSNPs combined with borneol could improve the anti-glioma efficacy with the prolonged medium survival time (39 days). In conclusion, the collaborative strategy of CGKRK-PSNPs combined with borneol provided a promising drug delivery routine for glioblastoma therapy.https://www.frontiersin.org/article/10.3389/fphar.2020.00558/fullborneolblood-brain barrier penetrationpaclitaxelredox-responsive nanoparticlesCGKRK peptide |
| spellingShingle | Lingyan Lv Lingyan Lv Xinrui Li Xinrui Li Wei Qian Shennan Li Yan Jiang Yaokun Xiong Jianpei Xu Wei Lv Xiaoyan Liu Yun Chen Yulin Tang Hongliang Xin Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive Nanoparticles Frontiers in Pharmacology borneol blood-brain barrier penetration paclitaxel redox-responsive nanoparticles CGKRK peptide |
| title | Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive Nanoparticles |
| title_full | Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive Nanoparticles |
| title_fullStr | Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive Nanoparticles |
| title_full_unstemmed | Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive Nanoparticles |
| title_short | Enhanced Anti-Glioma Efficacy by Borneol Combined With CGKRK-Modified Paclitaxel Self-Assembled Redox-Sensitive Nanoparticles |
| title_sort | enhanced anti glioma efficacy by borneol combined with cgkrk modified paclitaxel self assembled redox sensitive nanoparticles |
| topic | borneol blood-brain barrier penetration paclitaxel redox-responsive nanoparticles CGKRK peptide |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00558/full |
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