Journal
NATURE NANOTECHNOLOGY
Volume 14, Issue 1, Pages 89-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41565-018-0319-4
Keywords
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Funding
- UNC/NC state
- Jonsson Comprehensive Cancer Center at UCLA
- Alfred P. Sloan Foundation (Sloan Research Fellowship)
- National Key R&D Program of China [2017YFA0205600]
- Program for Guangdong Introducing Innovative and Enterpreneurial Teams [2017ZT07S054]
- National Natural Science Foundation of China [51728301]
- UCLA
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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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