In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment

Qian Chen; Chao Wang; Xudong Zhang; Guojun Chen; Quanyin Hu; Hongjun Li; Jinqiang Wang; Di Wen; Yuqi Zhang; Yifei Lu; Guang Yang; Chen Jiang; Jun Wang; Gianpietro Dotti; Zhen Gu

doi:10.1038/s41565-018-0319-4

In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment

Nat Nanotechnol. 2019 Jan;14(1):89-97. doi: 10.1038/s41565-018-0319-4. Epub 2018 Dec 10.

Authors

Qian Chen^{1

2

3}, Chao Wang³, Xudong Zhang^{1

2}, Guojun Chen^{1

2}, Quanyin Hu^{1

2

3}, Hongjun Li⁴, Jinqiang Wang³, Di Wen^{1

2}, Yuqi Zhang³, Yifei Lu^{3

5}, Guang Yang^{1

2}, Chen Jiang⁵, Jun Wang⁴, Gianpietro Dotti⁶, Zhen Gu^{7

8

9

10

11}

Affiliations

¹ Department of Bioengineering, University of California, Los Angeles, CA, USA.
² California NanoSystems Institute, University of California, Los Angeles, CA, USA.
³ Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA.
⁴ National Engineering Research Center for Tissue Restoration and Reconstruction, and School of Biomedical Science and Engineering, South China University of Technology, Guangzhou, Guangdong, China.
⁵ 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.
⁶ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
⁷ Department of Bioengineering, University of California, Los Angeles, CA, USA. guzhen@ucla.edu.
⁸ California NanoSystems Institute, University of California, Los Angeles, CA, USA. guzhen@ucla.edu.
⁹ Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. guzhen@ucla.edu.
¹⁰ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. guzhen@ucla.edu.
¹¹ Center for Minimally Invasive Therapeutics, University of California, Los Angeles, CA, USA. guzhen@ucla.edu.

PMID: 30531990
DOI: 10.1038/s41565-018-0319-4

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biocompatible Materials / chemistry*
Calcium Carbonate / chemistry
Female
Fibrin / chemistry
Gels / chemistry*
Humans
Immunity
Immunotherapy / methods*
Luminescent Measurements
Melanoma, Experimental / pathology
Mice, Inbred C57BL
Nanoparticles / chemistry
Nanoparticles / ultrastructure
Neoplasm Recurrence, Local / pathology
Neoplasms / pathology
Neoplasms / surgery*
Phagocytosis

Substances

Biocompatible Materials
Gels
Fibrin
Calcium Carbonate