不完全手术切除（SR）后的肿瘤促进生态位可通过增强的血管生成-免疫抑制肿瘤微环境（TME）导致更具侵袭性的局部进展和远处转移。在此，中性粒细胞胞外陷阱（NET）和癌症相关神经递质（CANT，例如儿茶酚胺）升高首先被确定为两个主要诱因。此外，还构建了一种具有高组织粘附力的可注射纤维蛋白-海藻酸盐水凝胶，可特异性地共同递送 NETs 抑制剂（DNase I）封装的 PLGA 纳米颗粒和非选择性 β-肾上腺素能受体阻滞剂（普萘洛尔）。这两种成分（即纤维蛋白和海藻酸盐）可以在术后出血中响应两种触发因素（分别是凝血酶和Ca2+），形成凝胶，形成具有高强度的互穿网络（IPN）。 DNase I 和 PR 的持续释放可以破坏 NET 并拮抗儿茶酚胺，从而降低微血管密度、阻断骨髓源性抑制细胞、分泌各种促炎细胞因子、增强自然杀伤细胞功能并阻碍细胞毒性 T 细胞耗竭。重编程的TME显着抑制局部残留和远处肿瘤，诱导强烈的免疫记忆效应，从而抑制肺转移。因此，通过这种基于 IPN 的原位水凝胶药物库实现有针对性地降解 NET 和阻断 CANT，提供了一种简单有效的方法来对抗 SR 诱导的癌症复发和转移。© 2024 作者。

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective β-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.© 2024 The Authors.