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

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

Bioactive Materials (Sep 2024)

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

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

Affiliations

Hang Zhou: In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Surgeons' Hall, No.246. XuefuRoad, Nangang District, Harbin City, Heilongjiang Prov, PR China
Chunyan Zhu: 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China; Ultrasound Research and Education Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai, 200072, PR China
Qing Zhao: In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Surgeons' Hall, No.246. XuefuRoad, Nangang District, Harbin City, Heilongjiang Prov, PR China
Jinliang Ni: 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China; Ultrasound Research and Education Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai, 200072, PR China
Haipeng Zhang: 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China; Ultrasound Research and Education Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai, 200072, PR China
Guangcan Yang: 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China; Ultrasound Research and Education Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai, 200072, PR China
Jianchao Ge: 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China
Chao Fang: 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China
Hong Wei: In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Surgeons' Hall, No.246. XuefuRoad, Nangang District, Harbin City, Heilongjiang Prov, PR China
Xianli Zhou: In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Surgeons' Hall, No.246. XuefuRoad, Nangang District, Harbin City, Heilongjiang Prov, PR China; Corresponding author.
Kun Zhang: 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China; Ultrasound Research and Education Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai, 200072, PR China; Corresponding author. 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 China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China.

Journal volume & issue: Vol. 39
pp. 14 – 24

Abstract

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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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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