4.5 Article

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

Journal

CHINESE JOURNAL OF POLYMER SCIENCE
Volume 40, Issue 5, Pages 491-503

Publisher

SPRINGER
DOI: 10.1007/s10118-022-2695-3

Keywords

GBM; PDCs; WBPU; Scaffolds; Controlled release

Funding

  1. Key Program of National Natural Science Foundation of China [51733005]
  2. General Program of the National Natural Science Foundation of China [51873122]
  3. National Natural Science Foundation [81902549]
  4. Key research and development project of science and technology department of Sichuan Province [2021YFS0202]
  5. Postdoctoral Research Fund of West China Hospital [2019HXBH056]

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In this study, waterborne biodegradable polyurethane (WBPU) scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel (PTX) polymer-drug conjugates (PDCs) were developed for targeted GBM therapy. The dual-targeting PTX-PDC-loaded scaffolds exhibited significant anti-GBM effects and normal tissue protection simultaneously, indicating a promising strategy for local therapy of GBM.
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.

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