肿瘤细胞在与细胞外基质（ECM）分离或失去细胞间连接时可以存活，这种现象称为失巢凋亡抵抗（AR）。 AR与肿瘤细胞的转移和复发密切相关，使肿瘤细胞在脱离后进行播散、迁移和侵袭。为了解决这个问题，人们提出了一种将术中止血与多功能纳米酶驱动的增强化学动力学疗法（ECDT）相结合的新干预方法，该方法具有削弱肿瘤细胞的AR能力并抑制肿瘤复发的潜力。在这里，在表面 PEG 接枝和葡萄糖氧化酶 (GOx) 锚定 (DMSN-Cu@GOx/PEG) 后，使用阴离子辅助方法开发了一种含有 Cu2 的树枝状介孔纳米框架的纳米复合材料。 DMSN-Cu@GOx/PEG 进一步封装在热敏水凝胶（H@DMSN-Cu@GOx/PEG）中。 DMSN-Cu@GOx/PEG利用其高过氧化物酶（POD）活性来提高细胞内ROS水平，从而削弱膀胱癌细胞的AR能力。此外，DMSN-Cu@GOx/PEG通过其优异的过氧化氢酶（CAT）活性，将细胞内GOx催化的高水平过氧化氢（H2O2）转化为氧气（O2），有效缓解肿瘤缺氧，下调缺氧诱导因子1α （HIF-1α）表达，抑制上皮间质转化（EMT）过程，最终抑制膀胱癌细胞的迁移和侵袭。有趣的是，体内结果表明，热敏水凝胶H@DMSN-Cu@GOx/PEG可以在体温下快速胶凝，在伤口上形成凝胶膜，以消除肿瘤切除手术后残留的肿瘤组织。重要的是，H@DMSN-Cu@GOx/PEG表现出优异的止血能力，有效增强肿瘤切除术后的组织凝固，降低手术出血引起的癌细胞扩散和复发的风险。这种水凝胶无疑具有很强的外科应用价值。我们开发的新型纳米系统和水凝胶可以抑制肿瘤细胞的 AR 能力并防止术后复发。这项研究首次报道了使用树枝状介孔二氧化硅基纳米反应器抑制膀胱癌细胞的 AR 能力并抑制肿瘤术后复发，为制定阻止肿瘤术后复发的策略提供了新途径。© 2024。作者（s）。

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell-cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.© 2024. The Author(s).