Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme

He-Cheng Wu; Yuan Feng; Xing-Ying Song; Chun-Yang Song; Jin-Lin Chen; Yan-Chao Wang; Xue-Ling He; Rui-Chao Liang; Jie-Hua Li; Hong Tan

doi:10.1007/s10118-022-2695-3

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Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme

RESEARCH ARTICLE | Updated：2022-04-26

- Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme
- Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme
- Chinese Journal of Polymer Science 2022年40卷第5期页码：491-503
- Affiliations：
  
  a.College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
  b.Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China
  c.Laboratory Animal Center of Sichuan University, Chengdu 610041, China
- Author bio：
  
  dr_liangruichao@scu.edu.cn (R.C.L.)
  hongtan@scu.edu.cn (H.T.)
- Funds：
  
  This work was financially supported by Key Program of National Natural Science Foundation of China (No. 51733005), General Program of the National Natural Science Foundation of China (No. 51873122), National Natural Science Foundation for Young Scholars (No. 81902549), Key research and development project of science and technology department of Sichuan Province (No. 2021YFS0202) and Postdoctoral Research Fund of West China Hospital (No. 2019HXBH056).
- DOI：10.1007/s10118-022-2695-3
  中图分类号：
- 收稿：2021-11-11，
  
  修回：2022-1-4，
  
  录用：2022-1-12，
  
  网络首发：2022-03-21，
  
  纸质出版：2022-05-01
- Accepted：
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Wu, H. C.; Feng, Y.; Song, X. Y.; Song, C. Y.; Chen, J. L.; Wang, Y. C.; He, X. L.; Liang, R. C.; Li, J. H.; Tan, H. Implantable polyurethane scaffolds loading with PEG-paclitaxel conjugates for the treatment of glioblastoma multiforme. Chinese J. Polym. Sci. 2022, 40, 491–503

He-Cheng Wu, Yuan Feng, Xing-Ying Song, et al. Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme[J]. Chinese Journal of Polymer Science, 2022, 40(5): 491-503.
Wu, H. C.; Feng, Y.; Song, X. Y.; Song, C. Y.; Chen, J. L.; Wang, Y. C.; He, X. L.; Liang, R. C.; Li, J. H.; Tan, H. Implantable polyurethane scaffolds loading with PEG-paclitaxel conjugates for the treatment of glioblastoma multiforme. Chinese J. Polym. Sci. 2022, 40, 491–503 DOI： 10.1007/s10118-022-2695-3.

He-Cheng Wu, Yuan Feng, Xing-Ying Song, et al. Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme[J]. Chinese Journal of Polymer Science, 2022, 40(5): 491-503. DOI： 10.1007/s10118-022-2695-3.

摘要

Abstract

Improvement of the treatment for Glioblastoma multiforme (GBM) especially the development of

in situ

controllable drug release is still a major concern. In this study

we developed waterborne biodegradable polyurethane (WBPU) scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel (PTX) polymer-drug conjugates (PDCs) for targeted GBM therapy

in situ

. The drug scaffolds could be implanted at residual GBM site post-operation. Dual-targeting PTX-PDCs were obtained through step-by-step conjugation of disulfide linked PTX

poly(ethylene glycol) (PEG)

and arginine-glycine-aspartic acid (RGD). The RGD-modified PTX-PDCs were spherical nanoparticles (NPs) that would be released from scaffolds and identified GBM cells actively. Internalized redox-sensitive PTX-PDCs would be decomposed and release PTX inside GBM cells under the circumstances of glutathione (GSH). The release profiles of PTX from the scaffolds with/without GSH were investigated.

In vitro

cytotoxicity assay revealed that the dual-targeting PTX-PDCs from scaffolds could specifically kill GBM cells and protect normal cells

suggesting that dual-targeting PTX-PDC-loaded scaffolds may have the potential to repair tumor-induced brain injury.

In vivo

anti-recurrence assay indicated that the PTX-PDC-scaffolds could deliver PTX-PDCs to the GBM cells followed by inhibiting tumor growth and inducing apoptosis. In general

the PTX prodrug-loaded devices exhibited significant anti-GBM effects and normal tissue protection simultaneously

indicating that the WBPU scaffolds incorporated with dual-targeting PTX-PDCs may be a promising strategy for local therapy of GBM.

关键词

Keywords

references

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