Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages
Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted suppression of the NLRP3 inflammasome shows promise in reducing macrophage inflamm...
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0581 |
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| author | Jiayi Mao Wenzheng Xia Yanglin Wu Minxiong Li Yun Zhao Peisong Zhai Yuguang Zhang Tao Zan Wenguo Cui Xiaoming Sun |
| author_facet | Jiayi Mao Wenzheng Xia Yanglin Wu Minxiong Li Yun Zhao Peisong Zhai Yuguang Zhang Tao Zan Wenguo Cui Xiaoming Sun |
| author_sort | Jiayi Mao |
| collection | DOAJ |
| description | Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted suppression of the NLRP3 inflammasome shows promise in reducing macrophage inflammatory disruptions. However, challenges such as drug off-target effects and degradation via lysosomal capture remain during treatment. In this study, engineered apoptotic bodies (BHB-dABs) derived from adipose stem cells loaded with β-hydroxybutyric acid (BHB) were synthesized via biosynthesis. These vesicles target M1-type macrophages, which highly express the folic acid receptor in the inflammatory microenvironment, and facilitate lysosomal escape through 1,2-distearoyl-sn-propyltriyl-3-phosphatidylethanolamine–polyethylene glycol functionalization, which may enhance the efficacy of NLRP3 inhibition for managing diabetic wounds. In vitro studies demonstrated the biocompatibility of BHB-dABs, their selective targeting of M1-type macrophages, and their ability to release BHB within the inflammatory microenvironment via folic acid and folic acid receptor signaling. These nanovesicles exhibited lysosomal escape, anti-inflammatory, mitochondrial protection, and endothelial cell vascularization properties. In vivo experiments demonstrated that BHB-dABs enhance the recovery of diabetic wound inflammation and angiogenesis, accelerating wound healing. These functionalized apoptotic bodies efficiently deliver NLRP3 inflammasome inhibitors using a dual strategy of targeting macrophages and promoting lysosomal escape. This approach represents a novel therapeutic strategy for effectively treating chronic diabetic wounds. |
| format | Article |
| id | doaj-art-f900d2f49b5b4407af7967d15b6cfefb |
| institution | Kabale University |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-f900d2f49b5b4407af7967d15b6cfefb2025-01-23T08:00:57ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0581Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in MacrophagesJiayi Mao0Wenzheng Xia1Yanglin Wu2Minxiong Li3Yun Zhao4Peisong Zhai5Yuguang Zhang6Tao Zan7Wenguo Cui8Xiaoming Sun9Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.Department of Orthopaedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P. R. China.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted suppression of the NLRP3 inflammasome shows promise in reducing macrophage inflammatory disruptions. However, challenges such as drug off-target effects and degradation via lysosomal capture remain during treatment. In this study, engineered apoptotic bodies (BHB-dABs) derived from adipose stem cells loaded with β-hydroxybutyric acid (BHB) were synthesized via biosynthesis. These vesicles target M1-type macrophages, which highly express the folic acid receptor in the inflammatory microenvironment, and facilitate lysosomal escape through 1,2-distearoyl-sn-propyltriyl-3-phosphatidylethanolamine–polyethylene glycol functionalization, which may enhance the efficacy of NLRP3 inhibition for managing diabetic wounds. In vitro studies demonstrated the biocompatibility of BHB-dABs, their selective targeting of M1-type macrophages, and their ability to release BHB within the inflammatory microenvironment via folic acid and folic acid receptor signaling. These nanovesicles exhibited lysosomal escape, anti-inflammatory, mitochondrial protection, and endothelial cell vascularization properties. In vivo experiments demonstrated that BHB-dABs enhance the recovery of diabetic wound inflammation and angiogenesis, accelerating wound healing. These functionalized apoptotic bodies efficiently deliver NLRP3 inflammasome inhibitors using a dual strategy of targeting macrophages and promoting lysosomal escape. This approach represents a novel therapeutic strategy for effectively treating chronic diabetic wounds.https://spj.science.org/doi/10.34133/research.0581 |
| spellingShingle | Jiayi Mao Wenzheng Xia Yanglin Wu Minxiong Li Yun Zhao Peisong Zhai Yuguang Zhang Tao Zan Wenguo Cui Xiaoming Sun Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages Research |
| title | Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages |
| title_full | Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages |
| title_fullStr | Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages |
| title_full_unstemmed | Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages |
| title_short | Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages |
| title_sort | biosynthesis of lysosomally escaped apoptotic bodies inhibits inflammasome synthesis in macrophages |
| url | https://spj.science.org/doi/10.34133/research.0581 |
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