Abstract：
Adapting the mechanical strength between the implant materials and the brain tissue is crucial for the postoperative treatment of glioblastoma. However, no related study has been reported. Herein, we report an injectable lipoic acid‑iron (LA-Fe) hydrogel (LFH) that can adapt to the mechanical strength of various brain tissues, including human brain tissue, by coordinating Fe3+ into a hybrid hydrogel of LA and its sodium salt (LANa). When LFH, which matches the mechanical properties of mouse brain tissue (337 ± 8.06 Pa), was injected into the brain resection cavity, the water content of the brain tissue was maintained at a normal level (77%). Similarly, LFH did not induce the activation or hypertrophy of glial astrocytes, effectively preventing brain edema and scar hyperplasia. Notably, LFH spontaneously degrades in the interstitial fluid, releasing LA and Fe3+ into tumor cells. The redox couples LA/DHLA (dihydrolipoic acid, reduction form of LA in cells) and Fe3+/Fe2+ would regenerate each other to continuously provide ROS to induce ferroptosis and activate immunogenic cell death. As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the efficacy of tumor-immunotherapy and promoted tumor ferroptosis. The injectable hydrogel that adapted the mechanical strength of tissues shed a new light for the tumor postoperative treatment.
摘要：
适应植入材料与脑组织之间的机械强度对于胶质母细胞瘤的术后治疗至关重要。然而,没有相关研究的报道。在这里，我们报告了一种可注射的硫辛酸-铁（LA-Fe）水凝胶（LFH），可以适应各种脑组织的机械强度，包括人类的脑组织,通过将Fe3+配位到LA及其钠盐(LANa)的混合水凝胶中。当LFH,与小鼠脑组织的机械性能（337±8.06Pa）相匹配，被注射到大脑切除腔中，脑组织含水量维持在正常水平(77%)。同样，LFH不诱导神经胶质细胞的活化或肥大，有效预防脑水肿和瘢痕增生。值得注意的是,LFH在间质液中自发降解，将LA和Fe3+释放到肿瘤细胞中。氧化还原对LA/DHLA（二氢硫辛酸，细胞中LA的还原形式）和Fe3/Fe2会彼此再生以连续提供ROS以诱导铁凋亡并激活免疫原性细胞死亡。随着抗PDL1的负载，抗PDL1@LFH进一步增强了肿瘤免疫疗法的功效并促进了肿瘤的铁凋亡。适应组织机械强度的可注射水凝胶为肿瘤术后治疗提供了新的思路。
