Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the ‘don’t eat me’ signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel ‘awakens’ the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.
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The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.
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This work was supported by grants from start-up packages from UNC/NC state and UCLA, the Jonsson Comprehensive Cancer Center at UCLA, the Alfred P. Sloan Foundation (Sloan Research Fellowship), the National Key R&D Program of China (2017YFA0205600), the Program for Guangdong Introducing Innovative and Enterpreneurial Teams (2017ZT07S054) and the National Natural Science Foundation of China (51728301). The authors thank L. Huang at UNC at Chapel Hill for providing the B16F10-Luc-GFP.
Z.G. and Q.C. have applied for patents related to this study. Z.G. is a scientific co-founder of ZenCapsule Inc.
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Chen, Q., Wang, C., Zhang, X. et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nature Nanotech 14, 89–97 (2019). https://doi.org/10.1038/s41565-018-0319-4
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