STING Membrane Prevents Post-Surgery Tissue Adhesion and Tumor Recurrence of Colorectal Cancer

Jianlin Li, Haiwang Yu, Yan Kang, Kun Niu, Ming Wang, Yitong Jiang,Ni Jiang,Zhenshan Ding,Zhihua Gan,Qingsong Yu

ADVANCED MATERIALS(2024)

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摘要
Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post-surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long-term surviving of CRC patients. To overcome CRC recurrence and avoid the post-surgery tissue adhesion, this work develops a novel stimulator of interferon genes "STING" membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core-shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. As-designed "STING" membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post-surgery tissue adhesion, facilitating the clinical intervention of CRC. Novel stimulator of interferon genes "STING" membrane is developed to overcome colorectal cancer recurrence and post-surgery tissue adhesion. The gambogic acid prodrug and STING agonist are continuously released from the core and shell layers, respectively, efficiently inducing immunogenic cell death of cancer cells and evoking the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. image
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关键词
antiadhesive membrane,cGAS/STING pathway activation,colorectal cancer,immunogenic cell death,surgical resection
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