A super carbonate apatite (sCA) could deliver sufficient amounts of miRNA into the colorectum inflamed by dextran sodium sulfate (DSS) treatment

Purpose: A super carbonate apatite (sCA) nanoparticle is an in vivo pH-sensitive delivery system for siRNA and microRNA. These carriers accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Systemic administration of sCA incorporating siRNA and microRNA has demonstrated superb tumor suppressive effects in vivo. We recently observed that sCA could deliver abundant nucleic acids to the inflammatory sites in rheumatoid arthritis mouse model. Based on the success, we tried to examine whether sCA could deliver sufficient amounts of miRNA into the colorectum inflamed by dextran sodium sulfate (DSS) treatment. Methods: We performed a RNA sequencing analysis of the DSS-treated colon walls. DSS was administered for 4 days and sCA-miR-29a, sCA-miR-29b, sCA-NC-miR was injected on days 1, 2, 3. On day 4, colorectum was removed and the mRNA samples were subject to the RNA sequencing analysis. Results: RNA sequencing of the rectum samples showed a number of enhanced or reduced gene expression in DSS treated NC-miR group on day 4 compared to normal mice. Such tendency of upregulation or downregulation was also noted in DSS-treated NC-miR group on day 2. Comparison of DSS treated samples on day 4 among NC-miR, miR-29a and miR-29b groups, revealed that several gene expression related to the interferon pathway was reversed by miR-29a or miR-29b towards the normal controls. These include Stat1, Stat2, IRF7, IRF9, and IFIT1. Conclusions: Many molecules in the interferon signaling pathway were activated in DSS-induced colitis on day 4 and Stat1, Stat2, IRF7, IRF9, and IFIT1 were key molecules in the interferon related pathways. These findings suggest that sCA-miR-29a or sCA-miR-29b may inhibit type 1 IFN and type 2 IFN pathways which are otherwise activated by DSS treatment. Overall design: ?iR-29a and miR-29b, NC-miR loaded in sCA were systemically administered from the tail vein on the 1st, 2nd and 3rd days after the 2% DSS administration was started, and the rectum of the mouse was collected on the 4th day. RNA was extracted from the harvested colorectum. For these four conditions (n = 2) and normal mice (n = 2), ten samples were subjected to RNA sequencing.

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Fukata T, Mizushima T, Nishimura J, Okuzaki D, Wu X, Hirose H, Yokoyama Y, Kubota Y, Nagata K, Tsujimura N, Inoue A, Miyoshi N, Haraguchi N, Takahashi H, Hata T, Matsuda C, Kayama H, Takeda K, Doki Y, Mori M, Yamamoto H