title: Correlation of the composition of biominerals with their ability of stimulating intracellular DNA sensors and inflammatory cytokines.
abstract: Biominerals (or microcalcification) deposited in soft tissues are associated with a number of pathogeneses and cancer progressions. Biominerals have also shown promise for DNA delivery and tissue engineering. Biominerals themselves may stimulate NALP3 inflammasomes, and DNA delivered by biominerals can potentially engage with intracellular DNA sensors, resulting in unwanted inflammatory responses. In this study, a library of biominerals doped with or without DNA is formed through surface-induced biomineralization. It is demonstrated that empty biominerals stimulate NALP3 inflammasomes and induce the production of IL-1β. They are also able to activate mouse embryonic fibroblasts (MEFs) and induce inflammatory cytokines, i.e. IL-6. DNA delivered by biominerals escapes the detection of TLR9, but activates DAI and inflammasomes. Furthermore, it is shown that the level of both IL-1β and IL-6 is correlated with the composition of biominerals, in particular the ratio of Mg(Sr) to Ca, and the pH sensitivity of biominerals. These results provide insights into the design of safe and effective DNA delivery systems and biocompatible implants as well as the understanding of the pathogeneses of biominerals deposited in soft tissues.
authors.affiliation: Department of Chemical Engineering, University of Washington, Campus Box 351750, Seattle, WA 98195, USA.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Sun
authors.affiliation: Elsa Biologics, LLC, Box 25725, WA 98165, USA. Electronic address: hong.shen@elsa-biologics.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D051379:Mice; D008903:Minerals / Q000276:immunology*; D013223:Statistics as Topic
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D008903:Minerals; D004247:DNA
keywords: Cancer therapy; Gene therapy; Implant rejection; Intracellular DNA sensors; Vaccines