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

作     者：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 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

作者机构：College of Polymer Science and EngineeringState Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China Department of NeurosurgeryWest China HospitalSichuan UniversityChengdu 610041China Laboratory Animal Center of Sichuan UniversityChengdu 610041China 

出 版 物：《Chinese Journal of Polymer Science》 (高分子科学（英文版）)

年 卷 期：2022年第40卷第5期

页      面：491-503页

核心收录：

学科分类：1002[医学-临床医学] 08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 0703[理学-化学] 10[医学] 

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) 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) 

主　　题：GBM PDCs WBPU Scaffolds Controlled release 

摘      要：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.