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Oral TNF-αsiRNA delivery via milk-derived exosomes for effective treatment of inflammatory bowel disease

Bioactive Materials 2024年第4期34卷 138-149页

作者： Geonhee Han hyosuk kim Hochung Jang Eun Sun kim Sun Hwa kim Yoosoo Yang KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul02792Republic of Korea Division of Bio-Medical Science and Technology KIST SchoolUniversity of Science and TechnologySeoul02792Republic of Korea Department of Internal Medicine Korea University College of MedicineSeoul02841Republic of Korea

Oral administration facilitates the direct delivery of drugs to lesions within the small intestine and colon,making it an ideal approach for treating patients with inflammatory bowel ***,multiple physical barriers impede the delivery of oral RNA drugs through the gastrointestinal ***,we developed a novel oral siRNA delivery system that protects nucleic acids in extreme environments by employing exosomes derived from milk to encapsulate tumor necrosis factor-alpha(TNF-α)siRNA *** remarkable structural stability of milk-derived exosomes(M-Exos),as opposed to those from HEK293T cells,makes them exceptional siRNA *** demonstrate that milk exosomes loaded with TNF-αsiRNA(M-Exo/siR)can effectively inhibit the expression of TNF-α-related inflammatory ***,given that milk exosomes are composed of unique lipids with high bioavailability,orally administered M-Exo/siR effectively reach colonic tissues,leading to decreased TNF-αexpression and successful alleviation of colitis symptoms in a dextran sulfate sodium-induced inflammatory bowel disease murine ***,milk-derived exosomes carrying TNF-αsiRNA can be effectively employed to treat inflammatory bowel ***,using exosomes naturally derived from milk may shift the current paradigm of oral gene delivery,including siRNA.

关键词： Milk-derived exosome Oral gene delivery siRNA Inflammatory bowel disease TNF-α

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Exosome-guided direct reprogramming of tumor-associated macrophages from protumorigenic to antitumorigenic to fight cancer

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Bioactive Materials 2023年第7期25卷 527-540页

作者： hyosuk kim Hyun-Ju Park Hyo Won Chang Ji Hyun Back Su Jin Lee Yae Eun Park Eun Hye kim Yeonsun Hong Gijung Kwak Ick Chan Kwon Ji Eun Lee Yoon Se Lee Sang Yoon kim Yoosoo Yang Sun Hwa kim Medicinal Materials Research Center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea Department of Functional Genomics KRIBB School of BioscienceKorea University of Science and Technology(UST)Daejeon34141Republic of Korea Department of Otolaryngology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul05505Republic of Korea Chemical&Biological Integrative Research Center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea Department of Biotechnology College of Life Sciences and BiotechnologyKorea UniversitySeoul02841Republic of Korea Department of Life Sciences Korea UniversitySeoul02841Republic of Korea

Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment *** particular,tumor-associated macrophages(TAMs),as the predominant infiltrated immune cells in a tumor,play a pivotal role in regulating the immunosuppressive tumor *** a potential therapeutic strategy to counteract TAMs,here we explore an exosome-guided in situ direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type *** derived from M1-type macrophages(M1-Exo)promote a phenotypic switch from anti-inflammatory M2-like TAMs toward pro-inflammatory M1-type macrophages with high conversion *** M1 macrophages possessing protein-expression profiles similar to those of classically activated M1 macrophages display significantly increased phagocytic function and robust cross-presentation ability,potentiating antitumor immunity surrounding the ***,these M1-Exo also lead to the conversion of human patient-derived TAMs into M1-like macrophages that highly express MHC class II,offering the clinical potential of autologous and allogeneic exosome-guided direct TAM reprogramming for arming macrophages to join the fight against cancer.

关键词： Exosome Cancer therapy Tumor microenvironment Tumor-associated macrophage Direct conversion

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