Chen et al. developed an in situ-formed biodegradable gel comprising biocompatible fibrinogen and thrombin, as well as calcium carbonate nanoparticles that scavenge H+ and slowly release encapsulated anti-CD47 to block the “don’t eat me” signal on tumor cells. When sprayed onto an incomplete tumor resection site, the gel reduced the acidity of the TME (thus promoting M1-polarization of TAMs), enhanced phagocytosis of tumor cells by macrophages and DCs, and mounted a systemic immune response, resulting in inhibition of local and distant tumor growth. Tumors showed an increase in TILs and a decrease in intratumoral MDSCs and Tregs.

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.

Author Info: (1) Department of Bioengineering, University of California, Los Angeles, CA, USA. California NanoSystems Institute, University of California, Los Angeles, CA, USA. Joint Department of Biomedical

Author Info: (1) Department of Bioengineering, University of California, Los Angeles, CA, USA. California NanoSystems Institute, University of California, Los Angeles, CA, USA. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. (2) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. (3) Department of Bioengineering, University of California, Los Angeles, CA, USA. California NanoSystems Institute, University of California, Los Angeles, CA, USA. (4) Department of Bioengineering, University of California, Los Angeles, CA, USA. California NanoSystems Institute, University of California, Los Angeles, CA, USA. (5) Department of Bioengineering, University of California, Los Angeles, CA, USA. California NanoSystems Institute, University of California, Los Angeles, CA, USA. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. (6) National Engineering Research Center for Tissue Restoration and Reconstruction, and School of Biomedical Science and Engineering, South China University of Technology, Guangzhou, Guangdong, China. (7) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. (8) Department of Bioengineering, University of California, Los Angeles, CA, USA. California NanoSystems Institute, University of California, Los Angeles, CA, USA. (9) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. (10) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China. (11) Department of Bioengineering, University of California, Los Angeles, CA, USA. California NanoSystems Institute, University of California, Los Angeles, CA, USA. (12) Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China. (13) National Engineering Research Center for Tissue Restoration and Reconstruction, and School of Biomedical Science and Engineering, South China University of Technology, Guangzhou, Guangdong, China. (14) Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. (15) Department of Bioengineering, University of California, Los Angeles, CA, USA. guzhen@ucla.edu. California NanoSystems Institute, University of California, Los Angeles, CA, USA. guzhen@ucla.edu. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. guzhen@ucla.edu. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. guzhen@ucla.edu. Center for Minimally Invasive Therapeutics, University of California, Los Angeles, CA, USA. guzhen@ucla.edu.

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