Crystallinity of covalent organic frameworks controls immune responses
Biomaterials can act as pro- or anti-inflammatory agents. However, effects of biomaterials crystallinity on immune responses are poorly understood. We demonstrate that the adjuvant-like behaviour of covalent organic framework (COF) biomaterial is dependent on its crystallinity. COF crystallinity is inversely correlated with the activation of mouse and human dendritic cells (DC), but with antigen presentation by mouse DCs only. Amorphous COFs upregulates NFkB, TNF, and RIG-I signalling pathways, as well as the chemotaxis-associated gene Unc5c, when compared to crystalline COFs. Meanwhile, Unc5c inhibition disrupts the correlation between crystallinity and DC activation. Furthermore, COFs with the lowest crystallinity admixed with chicken ovalbumin (OVA) antigen prevent OVA-expressing B16F10 tumour growth in 60% of mice, with this protection associated with the induction of antigen-specific, pro-inflammatory T cell. The lowest crystalline COFs admixed with TRP2 antigen can also prevent non-immunogenic YUMM1.1 tumour growth in 50% of mice. These findings demonstrate that the crystallinity of biomaterials is an important aspect to consider when designing immunotherapy for pro- or anti-inflammatory applications.
Authors
- Taravat Khodaei
- Huikang Qian
- Abhirami Thumsi
- Julianne L. Holloway (ORCID: https://orcid.org/0000-0001-8508-3041)
- Srivatsan J. Swaminathan
- Abhirami P. Suresh (ORCID: https://orcid.org/0000-0003-0571-7919)
- Wei Sun (ORCID: https://orcid.org/0000-0003-3152-0124)
- Xinbo Tong (ORCID: https://orcid.org/0000-0003-3259-6374)
- Richard Nile (ORCID: https://orcid.org/0000-0003-1144-3045)
- Arezoo Esrafili (ORCID: https://orcid.org/0000-0001-6074-5395)
- Sanmoy Pathak
- Abhinav P. Acharya (ORCID: https://orcid.org/0000-0002-9361-2764)
- B J Kim (ORCID: https://orcid.org/0009-0006-7484-9340)
- Alicia Mathis (ORCID: https://orcid.org/0000-0001-7864-156X)
- Kelly Lintecum (ORCID: https://orcid.org/0000-0002-4968-2781)
- Yeo Weon Seo
- Kailong Jin (ORCID: https://orcid.org/0000-0001-5428-3227)
- Madhan Mohan Chandra Sekhar Jaggarapu (ORCID: https://orcid.org/0000-0002-1437-6311)
- Joshua Kupfer (ORCID: https://orcid.org/0009-0006-9306-3642)
- Margaret Dugoni
Institutions
- Arizona State University (US)
- Case Western Reserve University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1038/s41467-024-54227-9
- Citations
- 16
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 2.95
Funders
- National Aeronautics and Space Administration
- Case Western Reserve University
- Nuclear Safety and Security Commission
- National Institutes of Health
- American Chemical Society Petroleum Research Fund
- National Institute of Allergy and Infectious Diseases