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(WB...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.展开更多
基金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)+2 种基金National Natural Science Foundation for Young Scholars (No. 81902549)Key research and development project of science and technology department of Sichuan Province (No. 2021YFS0202)Postdoctoral Research Fund of West China Hospital (No. 2019HXBH056)
文摘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.
