In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting Osteoarthritis
There are still challenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation, due to the rapid clearance of nanocarriers and burst drug release in vivo. Herein, a nanomicelle–hydrogel microsphere, characterized by its macrophage-targeted nanosized secondary stru...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2023-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0131 |
| _version_ | 1797279665948196864 |
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| author | XiaoXiao Li Xingchen Li Jielai Yang Yawei Du Liang Chen Gang Zhao Tingjun Ye Yuan Zhu Xiangyang Xu Lianfu Deng Wenguo Cui |
| author_facet | XiaoXiao Li Xingchen Li Jielai Yang Yawei Du Liang Chen Gang Zhao Tingjun Ye Yuan Zhu Xiangyang Xu Lianfu Deng Wenguo Cui |
| author_sort | XiaoXiao Li |
| collection | DOAJ |
| description | There are still challenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation, due to the rapid clearance of nanocarriers and burst drug release in vivo. Herein, a nanomicelle–hydrogel microsphere, characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis, is employed for in situ sustained macrophage targeting and regulation, and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers. The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle, thus keeping it in joints, while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages, and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages. The experiments show that the nanomicelle–hydrogel microsphere can in situ sustainably target and regulate M1 macrophages for more than 14 days in joints, and attenuate local “cytokine storm” by continuous M1 macrophage apoptosis promotion and polarization inhibition. This micro/nano-hydrogel system shows excellent ability to sustainably target and regulate macrophage, realizes the improvement of drug utilization and efficacy inside the macrophage, and thereby can be a potential platform for treating macrophage-related diseases. |
| first_indexed | 2024-03-07T16:30:17Z |
| format | Article |
| id | doaj.art-2bc2f27672c348d1809f1b00f06d4b30 |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-03-07T16:30:17Z |
| publishDate | 2023-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-2bc2f27672c348d1809f1b00f06d4b302024-03-03T11:17:21ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742023-01-01610.34133/research.0131In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting OsteoarthritisXiaoXiao Li0Xingchen Li1Jielai Yang2Yawei Du3Liang Chen4Gang Zhao5Tingjun Ye6Yuan Zhu7Xiangyang Xu8Lianfu Deng9Wenguo Cui10Department 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, 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, 197 Ruijin 2nd Road, Shanghai 200025, P. R. China.There are still challenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation, due to the rapid clearance of nanocarriers and burst drug release in vivo. Herein, a nanomicelle–hydrogel microsphere, characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis, is employed for in situ sustained macrophage targeting and regulation, and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers. The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle, thus keeping it in joints, while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages, and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages. The experiments show that the nanomicelle–hydrogel microsphere can in situ sustainably target and regulate M1 macrophages for more than 14 days in joints, and attenuate local “cytokine storm” by continuous M1 macrophage apoptosis promotion and polarization inhibition. This micro/nano-hydrogel system shows excellent ability to sustainably target and regulate macrophage, realizes the improvement of drug utilization and efficacy inside the macrophage, and thereby can be a potential platform for treating macrophage-related diseases.https://spj.science.org/doi/10.34133/research.0131 |
| spellingShingle | XiaoXiao Li Xingchen Li Jielai Yang Yawei Du Liang Chen Gang Zhao Tingjun Ye Yuan Zhu Xiangyang Xu Lianfu Deng Wenguo Cui In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting Osteoarthritis Research |
| title | In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting Osteoarthritis |
| title_full | In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting Osteoarthritis |
| title_fullStr | In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting Osteoarthritis |
| title_full_unstemmed | In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting Osteoarthritis |
| title_short | In Situ Sustained Macrophage-Targeted Nanomicelle–Hydrogel Microspheres for Inhibiting Osteoarthritis |
| title_sort | in situ sustained macrophage targeted nanomicelle hydrogel microspheres for inhibiting osteoarthritis |
| url | https://spj.science.org/doi/10.34133/research.0131 |
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