한빛사논문
Mira Park1,4, Hyeon-Ji Oh2,4, Jieun Han2, Seok-Ho Hong3, Wooram Park2, Haengseok Song1
1Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi 13488, Republic of Korea
2Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Seoburo 2066, Suwon, Gyeonggi 16419, Republic of Korea
3Department of Internal Medicine, Kangwon National University, Chuncheon, Kangwon 24341, Republic of Korea
4These authors contributed equally
Corresponding authors: Wooram Park, PhD, Haengseok Song, PhD
Abstract
Macrophages are present in all tissues for maintaining tissue homeostasis, and macrophage polarization plays a vital role in alleviating inflammation. Therefore, specific delivery of polarization modulators to macrophages in situ is critical for treating inflammatory diseases. We demonstrate that a size-controlled miRNA-encapsulated macrophage-targeting liposomes (miR/MT-Lip) specifically targets macrophages to promote M1-to-M2 polarization conversion, alleviating inflammation without cytotoxicity. miR/MT-Lip, approximately 1.2 μm, showed excellent internalization through phagocytosis and/or macropinocytosis in macrophages. miR-10a/MT-Lip, but not scramble miR-Fluorescein amidite (FAM)/MT-Lip as control, effectively converted the polarization of lipopolysaccharide (LPS)-induced M1 macrophages to M2 in vitro. When miR-10a/MT-Lip was intravenously delivered to mice insulted with LPS for inflammation, the proportion of M2 macrophages was significantly increased without disturbing the population of other immune cells. Furthermore, scramble miR-FAM/MT-Lip was mainly detected in macrophages, but not other immune cells. When our miR/MT-Lip was administered to mice with Asherman’s syndrome that suffer from infertility because of sterile uterine inflammation, macrophage-specific targeting of miR-10a/MT-Lip facilitated M1-to-M2 conversion for angiogenesis in the impaired uterus, resulting in restoration of healthy uterine conditions. The results indicate that our MT-Lip encapsulating small RNAs has excellent potential to treat various inflammatory disorders by fine-tuning macrophage polarization in vivo without any side effects.
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