Assembled Embedded 3D Hydrogel System for Asynchronous Drug Delivery to Inhibit Postoperative Recurrence of Malignant Glioma and Promote Neurological Recovery

• Published in: Advanced functional materials 2024-07, Vol.34 (30), p.n/a
• Main Authors: Hu, Yang, Zhou, Liming, Wang, Zhenning, Ye, Zhiming, Liu, Huiling, Lu, Yi, Qi, Zhihui, Yang, Kunhua, Zeng, Jianhao, Li, Huimin, Tang, Ruizhe, Ren, Jiaoyan, Guo, Rui, Yao, Maojin
• Format: Article
• Language: English
• Subjects: 3D printing hydrogels; asynchronous drug delivery; Drug delivery systems; Gelatin; glioblastoma recurrence; Hydrogels; neurological deficits; Recovery; Tumors
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202401383

Surgical resection of glioblastoma multiforme (GBM) often results in tumor recurrence and mild neurologic deficits. Here, a 3D asynchronous drug delivery system is innovatively developed to address the dual challenges of GBM recurrence and postoperative neurological deficit. Based on transcriptome analysis of tumor cells and tumor microenvironment (TME) cells between primary and recurrent mouse GBM tissues, a novel dual‐targeting approach is developed to combine mTOR pathway inhibition with microglia/macrophage repolarization. Then, in situ injectable methacrylated gelatin (GelMA) is constructed to perfectly fit into the tumor resection cavity and achieve direct delivery of dual‐targeted drugs, exhibiting outstanding postoperative GBM inhibitory effects in vivo. At the same time, neurotrophic factor‐saturated 3D‐printed GelMA patches are used to construct a 3D asynchronous drug delivery system, allowing gradual penetration of the neurotrophic factors into the underlying hydrogel to promote axonal sprouting after GBM suppression. Notably, this 3D asynchronous drug delivery system promotes neurological recovery without weakening the efficacy of inhibiting tumor recurrence. Therefore, this study not only proposes a new dual‐targeted GBM treatment strategy but also pioneers the construction of a 3D asynchronous drug delivery system for the comprehensive treatment of GBM. This study is expected to improve the poor prognosis of patients with GBM. An asynchronous drug delivery 3D hydrogel system inhibits postoperative recurrence of malignant glioma and promotes neurological recovery. A, B) Schematic illustration of the preparation and formation of GelMA/TP and neurotrophins‐loaded GelMA patch (GelMA/TPNB). C) GelMA/TPNB is used to treat the GBM resection mouse model. D, E) Mechanism of GelMA/TPNB for postresection GBM relapse prevention and neurological recovery.