Crystallinity of covalent organic frameworks controls immune responses

Autor: Arezoo Esrafili, Abhirami Thumsi, Madhan Mohan Chandra Sekhar Jaggarapu, Richard G. Nile, Joshua Kupfer, Margaret Dugoni, Abhirami P. Suresh, Taravat Khodaei, Huikang Qian, Anna Mathis, Brandon Kim, Srivatsan J. Swaminathan, Wei Sun, Yeo Weon Seo, Kelly Lintecum, Sanmoy Pathak, Xinbo Tong, Julianne L. Holloway, Kailong Jin, Abhinav P. Acharya
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-54227-9
Popis: Abstract 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.
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