Crystallinity of covalent organic frameworks controls immune responses

• Published in: Nature communications 2024-11, Vol.15 (1), p.9739-14, Article 9739
• Main Authors: Esrafili, Arezoo, Thumsi, Abhirami, Jaggarapu, Madhan Mohan Chandra Sekhar, Nile, Richard G., Kupfer, Joshua, Dugoni, Margaret, Suresh, Abhirami P., Khodaei, Taravat, Qian, Huikang, Mathis, Anna, Kim, Brandon, Swaminathan, Srivatsan J., Sun, Wei, Seo, Yeo Weon, Lintecum, Kelly, Pathak, Sanmoy, Tong, Xinbo, Holloway, Julianne L., Jin, Kailong, Acharya, Abhinav P.
• Format: Article
• Language: English
• Subjects: 13/2; 13/31; 13/89; 631/61/54/1866; 631/67/1059/4042; 631/67/580; 639/166/985; Animal models; Animals; Anti-inflammatory agents; Antigen presentation; Antigen Presentation - immunology; Antigens; Biocompatible Materials - chemistry; Biomaterials; Biomedical materials; Cell activation; Chemotaxis; Correlation; Covalence; Crystallinity; Crystallization; Degree of crystallinity; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunogenicity; Immunotherapy; Inflammation; Lymphocytes; Lymphocytes T; Melanoma, Experimental - immunology; Metal-Organic Frameworks - chemistry; Mice; Mice, Inbred C57BL; multidisciplinary; NF-kappa B - metabolism; NF-κB protein; Ovalbumin; Ovalbumin - immunology; Science; Science (multidisciplinary); Signal Transduction; Tumor Necrosis Factor-alpha - metabolism; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54227-9

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. Effects of biomaterials crystallinity on immune response is poorly understood. Here the authors show that the degree of crystallinity determines adjuvant-like effects of covalent organic framework (COF) biomaterial, with lower crystallinity correlating with better anti-tumour effects in multiple mouse tumour models.