Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategy
Abstract Rheumatoid arthritis (RA) is an autoimmune disease whose pathophysiology is closely related to inflammation-associated cells and the microenvironment of inflamed joints. This study aimed to develop dual-targeted, reactive oxygen species (ROS)/pH dual-responsive, size-shrinkable intelligent...
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| Format: | Article |
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BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-03085-0 |
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| author | Rui-Bo Guo Lu Zhang Yang Liu Liang Kong Yang Yu Bin Yang Zuo-Jun Wang Jing-Yi Zhang Xue-Tao Li |
| author_facet | Rui-Bo Guo Lu Zhang Yang Liu Liang Kong Yang Yu Bin Yang Zuo-Jun Wang Jing-Yi Zhang Xue-Tao Li |
| author_sort | Rui-Bo Guo |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA) is an autoimmune disease whose pathophysiology is closely related to inflammation-associated cells and the microenvironment of inflamed joints. This study aimed to develop dual-targeted, reactive oxygen species (ROS)/pH dual-responsive, size-shrinkable intelligent micelles targeting M1 macrophages and fibroblast-like synoviocytes (FLSs) to enhance drug efficacy and safety. These micelles were surface-modified with PEG5000 to prolong their circulation time in the bloodstream and hide the targeting molecules. The optimized particle size allowed the micelles to reside in inflamed joints through the extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS) effect. The high concentration of ROS in the inflamed joint caused the detachment of the hydration layer of PEG5000, which was then specifically recognized and internalized by M1 macrophages and FLSs via CD44 receptor-mediated endocytosis, ultimately allowing the release of the drug into the acidic environment of the inflamed cells. The in vivo and in vitro evaluation showed that micelles precisely targeted the inflammatory site, thus inhibiting the expression of pro-inflammatory cytokines, reversing the polarization of M1 macrophages, inhibiting the invasion and migration of proliferative FLSs, and, at the same time, regulating the seeds and soils of RA. This “three birds with one stone” approach targeted multiple aspects of RA, opening new horizons for comprehensive treatment of RA. |
| format | Article |
| id | doaj-art-f45283f4131047bc8307274b0ed523e3 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-f45283f4131047bc8307274b0ed523e32025-02-02T12:41:13ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112110.1186/s12951-024-03085-0Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategyRui-Bo Guo0Lu Zhang1Yang Liu2Liang Kong3Yang Yu4Bin Yang5Zuo-Jun Wang6Jing-Yi Zhang7Xue-Tao Li8School of Pharmacy, Liaoning University of Traditional Chinese MedicineSchool of Pharmacy, Liaoning University of Traditional Chinese MedicineSchool of Pharmacy, Liaoning University of Traditional Chinese MedicineSchool of Pharmacy, Liaoning University of Traditional Chinese MedicineSchool of Pharmacy, Liaoning University of Traditional Chinese MedicineDepartment of Pharmacy, General Hospital of Northern Theater CommandDepartment of Pharmacy, General Hospital of Northern Theater CommandDepartment of Pharmacy, General Hospital of Northern Theater CommandSchool of Pharmacy, Liaoning University of Traditional Chinese MedicineAbstract Rheumatoid arthritis (RA) is an autoimmune disease whose pathophysiology is closely related to inflammation-associated cells and the microenvironment of inflamed joints. This study aimed to develop dual-targeted, reactive oxygen species (ROS)/pH dual-responsive, size-shrinkable intelligent micelles targeting M1 macrophages and fibroblast-like synoviocytes (FLSs) to enhance drug efficacy and safety. These micelles were surface-modified with PEG5000 to prolong their circulation time in the bloodstream and hide the targeting molecules. The optimized particle size allowed the micelles to reside in inflamed joints through the extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS) effect. The high concentration of ROS in the inflamed joint caused the detachment of the hydration layer of PEG5000, which was then specifically recognized and internalized by M1 macrophages and FLSs via CD44 receptor-mediated endocytosis, ultimately allowing the release of the drug into the acidic environment of the inflamed cells. The in vivo and in vitro evaluation showed that micelles precisely targeted the inflammatory site, thus inhibiting the expression of pro-inflammatory cytokines, reversing the polarization of M1 macrophages, inhibiting the invasion and migration of proliferative FLSs, and, at the same time, regulating the seeds and soils of RA. This “three birds with one stone” approach targeted multiple aspects of RA, opening new horizons for comprehensive treatment of RA.https://doi.org/10.1186/s12951-024-03085-0Rheumatoid arthritisM1 macrophagesFibroblast-like synoviocytesMicellesCelastrol |
| spellingShingle | Rui-Bo Guo Lu Zhang Yang Liu Liang Kong Yang Yu Bin Yang Zuo-Jun Wang Jing-Yi Zhang Xue-Tao Li Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategy Journal of Nanobiotechnology Rheumatoid arthritis M1 macrophages Fibroblast-like synoviocytes Micelles Celastrol |
| title | Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategy |
| title_full | Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategy |
| title_fullStr | Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategy |
| title_full_unstemmed | Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategy |
| title_short | Treatment of rheumatoid arthritis using dual-targeted and dual-response intelligent micelles: a “three birds with one stone” strategy |
| title_sort | treatment of rheumatoid arthritis using dual targeted and dual response intelligent micelles a three birds with one stone strategy |
| topic | Rheumatoid arthritis M1 macrophages Fibroblast-like synoviocytes Micelles Celastrol |
| url | https://doi.org/10.1186/s12951-024-03085-0 |
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