Wrecking neutrophil extracellular traps and antagonizing cancer-associated neurotransmitters by interpenetrating network hydrogels prevent postsurgical cancer relapse and metastases  

作　　者：Hang Zhou Chunyan Zhu Qing Zhao Jinliang Ni Haipeng Zhang Guangcan Yang Jianchao Ge Chao Fang Hong Wei Xianli Zhou Kun Zhang 

机构地区：[1]In-Patient Ultrasound Department,Second Affiliated Hospital of Harbin Medical University,Surgeons’Hall,No.246.XuefuRoad,Nangang District,Harbin City,Heilongjiang Prov,PR China [2]Department of Laboratory Medicine and Central Laboratory,Sichuan Academy of Medical Sciences,Sichuan Provincial People’s Hospital,School of Medicine,University of Electronic Science and Technology of Chin1,No.32,West Second Section,First Ring Road,Chengdu,610072,Sichuan,PR China [3]Ultrasound Research and Education Institute,Shanghai Tenth People’s Hospital,Tongji University School of Medicine,No.301 Yan-chang-zhong Road,Shanghai

出　　处：《Bioactive Materials》2024年第9期14-24,共11页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China for Youth Scholars(Grant No.82022033,82202241);Heilongjiang Postdoctoral Science Foundation(Grant No.LBH-Z21022),China Postdoctoral Science Foundation(Grant No.2022MD713749);Sichuan Provincial Science Foundation for Distinguished Young Scholars(24NSFJQ0038).

摘　　要：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 unselectiveβ-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.

关 键 词：Neutrophil extracellular traps Cancer-associated neurotransmitters Interpenetrating network hydrogels Postsurgical cancer relapse and metastases Immunosuppressive tumor microenvironment 

分 类 号：TQ427.26[化学工程]