Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells
Abstract Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the diseas...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02228-z |
| _version_ | 1797414126271594496 |
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| author | Juan Tang Tao Li Xiaojing Xiong Qiaoyun Yang Zedazhong Su Minming Zheng Qingwei Chen |
| author_facet | Juan Tang Tao Li Xiaojing Xiong Qiaoyun Yang Zedazhong Su Minming Zheng Qingwei Chen |
| author_sort | Juan Tang |
| collection | DOAJ |
| description | Abstract Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the disease progression. Therefore, a new and effective strategy that blocks atherosclerosis-associated inflammation is urgently needed to further reduce the risk. Colchicine, a potent anti-inflammatory medication, has shown great potential in the treatment of atherosclerosis, but its adverse effects have hampered its clinical application. Herein, we developed a novel delivery nanosystem encapsulated with colchicine (VHPK-PLGA@COL), which exhibited improved biosafety and sustained drug release along with the gradual degradation of PLGA and PEG as confirmed both in vitro and in vivo. Surface modification of the nanoparticles with the VHPK peptide ensured its capability to specifically target inflammatory endothelial cells and alleviate atherosclerotic plaque accumulation. In the ApoE − / − atherosclerotic mouse model, both colchicine and VHPK-PLGA@COL treatment significantly decreased the plaque area and enhanced plaque stability by blocking the NF-κB/NLRP3 pathways, while VHPK-PLGA@COL exhibited enhanced therapeutic effects due to its unique ability to target inflammatory endothelial cells without obvious long-term safety concerns. In summary, VHPK-PLGA@COL has the potential to overcome the key translational barriers of colchicine and open new avenues to repurpose this drug for anti-atherosclerotic therapy. |
| first_indexed | 2024-03-09T05:28:37Z |
| format | Article |
| id | doaj.art-b996c878bdb84c9e9f4178f64989e89a |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-09T05:28:37Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-b996c878bdb84c9e9f4178f64989e89a2023-12-03T12:35:04ZengBMCJournal of Nanobiotechnology1477-31552023-11-0121112310.1186/s12951-023-02228-zColchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cellsJuan Tang0Tao Li1Xiaojing Xiong2Qiaoyun Yang3Zedazhong Su4Minming Zheng5Qingwei Chen6Department of General Practice, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of General Practice, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of General Practice, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of General Practice, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of General Practice, The Second Affiliated Hospital of Chongqing Medical UniversityAbstract Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the disease progression. Therefore, a new and effective strategy that blocks atherosclerosis-associated inflammation is urgently needed to further reduce the risk. Colchicine, a potent anti-inflammatory medication, has shown great potential in the treatment of atherosclerosis, but its adverse effects have hampered its clinical application. Herein, we developed a novel delivery nanosystem encapsulated with colchicine (VHPK-PLGA@COL), which exhibited improved biosafety and sustained drug release along with the gradual degradation of PLGA and PEG as confirmed both in vitro and in vivo. Surface modification of the nanoparticles with the VHPK peptide ensured its capability to specifically target inflammatory endothelial cells and alleviate atherosclerotic plaque accumulation. In the ApoE − / − atherosclerotic mouse model, both colchicine and VHPK-PLGA@COL treatment significantly decreased the plaque area and enhanced plaque stability by blocking the NF-κB/NLRP3 pathways, while VHPK-PLGA@COL exhibited enhanced therapeutic effects due to its unique ability to target inflammatory endothelial cells without obvious long-term safety concerns. In summary, VHPK-PLGA@COL has the potential to overcome the key translational barriers of colchicine and open new avenues to repurpose this drug for anti-atherosclerotic therapy.https://doi.org/10.1186/s12951-023-02228-zAtherosclerosisColchicineNanoparticlesNF-κB/NLRP3 pathwaysInflammatory endothelial cells |
| spellingShingle | Juan Tang Tao Li Xiaojing Xiong Qiaoyun Yang Zedazhong Su Minming Zheng Qingwei Chen Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells Journal of Nanobiotechnology Atherosclerosis Colchicine Nanoparticles NF-κB/NLRP3 pathways Inflammatory endothelial cells |
| title | Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells |
| title_full | Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells |
| title_fullStr | Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells |
| title_full_unstemmed | Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells |
| title_short | Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells |
| title_sort | colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of nf κb nlrp3 pathways in inflammatory endothelial cells |
| topic | Atherosclerosis Colchicine Nanoparticles NF-κB/NLRP3 pathways Inflammatory endothelial cells |
| url | https://doi.org/10.1186/s12951-023-02228-z |
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