Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway
Abstract Background The imbalance of macrophage polarization plays a pivotal role in the progression of rheumatoid arthritis (RA). Reprogramming macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is considered a promising therapeutic strategy. Methods To address...
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2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03576-8 |
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| author | Yang Yu Liang Kong Rui-bo Guo Ya-ni Zhang Shu-tong Li Feng-yuan Zhang Xin Wang Yang Liu Xiu-Ying Li Xue-tao Li |
| author_facet | Yang Yu Liang Kong Rui-bo Guo Ya-ni Zhang Shu-tong Li Feng-yuan Zhang Xin Wang Yang Liu Xiu-Ying Li Xue-tao Li |
| author_sort | Yang Yu |
| collection | DOAJ |
| description | Abstract Background The imbalance of macrophage polarization plays a pivotal role in the progression of rheumatoid arthritis (RA). Reprogramming macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is considered a promising therapeutic strategy. Methods To address this challenge, Panax notoginseng polysaccharides (PNP) with varying molecular weights were chemically conjugated with deoxycholic acid (DC) to obtain amphiphilic conjugates (PNP-DC), which self-assembled into micelles (PNP-Ms). After screening for optimal molecular weight, folic acid (FA) was introduced onto the micelle surface, and Polyphyllin I (PPI) was encapsulated to form FA-modified, PPI-loaded micelles (FA-PPI-Ms) with macrophage-targeting capability. Results FA-PPI-Ms showed enhanced cellular uptake via FA receptor–mediated endocytosis and effectively eliminated reactive oxygen species (ROS), reduced inflammatory cytokine production, and exhibited good biosafety. In vivo, FA-PPI-Ms significantly alleviated joint swelling and inflammation in RA rat models. Mechanistic studies based on RNA sequencing and experimental validation revealed that FA-PPI-Ms suppressed the JAK2/STAT3 signaling pathway, thereby promoting M2 macrophage polarization and restoring the M1/M2 balance. Conclusion This study presents a novel FA-PPI-Ms delivery system for targeted macrophages. By modulating polarization through inhibition of JAK2/STAT3 signaling, the system offers a promising therapeutic strategy for RA and potentially other inflammatory diseases. |
| format | Article |
| id | doaj-art-2f39e32afb034422b6e657d1b76ac9f0 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-2f39e32afb034422b6e657d1b76ac9f02025-08-20T04:03:07ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123112410.1186/s12951-025-03576-8Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathwayYang Yu0Liang Kong1Rui-bo Guo2Ya-ni Zhang3Shu-tong Li4Feng-yuan Zhang5Xin Wang6Yang Liu7Xiu-Ying Li8Xue-tao Li9College of Pharmacy, Liaoning University of Traditional Chinese MedicineCollege of Pharmacy, Liaoning University of Traditional Chinese MedicineCollege of Pharmacy, Liaoning University of Traditional Chinese MedicineCollege of Pharmacy, Liaoning University of Traditional Chinese MedicineCollege of Pharmacy, Liaoning University of Traditional Chinese MedicineShanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese MedicineShanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese MedicineCollege of Pharmacy, Liaoning University of Traditional Chinese MedicineShanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese MedicineCollege of Pharmacy, Liaoning University of Traditional Chinese MedicineAbstract Background The imbalance of macrophage polarization plays a pivotal role in the progression of rheumatoid arthritis (RA). Reprogramming macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is considered a promising therapeutic strategy. Methods To address this challenge, Panax notoginseng polysaccharides (PNP) with varying molecular weights were chemically conjugated with deoxycholic acid (DC) to obtain amphiphilic conjugates (PNP-DC), which self-assembled into micelles (PNP-Ms). After screening for optimal molecular weight, folic acid (FA) was introduced onto the micelle surface, and Polyphyllin I (PPI) was encapsulated to form FA-modified, PPI-loaded micelles (FA-PPI-Ms) with macrophage-targeting capability. Results FA-PPI-Ms showed enhanced cellular uptake via FA receptor–mediated endocytosis and effectively eliminated reactive oxygen species (ROS), reduced inflammatory cytokine production, and exhibited good biosafety. In vivo, FA-PPI-Ms significantly alleviated joint swelling and inflammation in RA rat models. Mechanistic studies based on RNA sequencing and experimental validation revealed that FA-PPI-Ms suppressed the JAK2/STAT3 signaling pathway, thereby promoting M2 macrophage polarization and restoring the M1/M2 balance. Conclusion This study presents a novel FA-PPI-Ms delivery system for targeted macrophages. By modulating polarization through inhibition of JAK2/STAT3 signaling, the system offers a promising therapeutic strategy for RA and potentially other inflammatory diseases.https://doi.org/10.1186/s12951-025-03576-8Rheumatoid arthritisPanax Notoginseng polysaccharideMicellesMacrophage polarizationJAK2-STAT3 |
| spellingShingle | Yang Yu Liang Kong Rui-bo Guo Ya-ni Zhang Shu-tong Li Feng-yuan Zhang Xin Wang Yang Liu Xiu-Ying Li Xue-tao Li Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway Journal of Nanobiotechnology Rheumatoid arthritis Panax Notoginseng polysaccharide Micelles Macrophage polarization JAK2-STAT3 |
| title | Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway |
| title_full | Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway |
| title_fullStr | Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway |
| title_full_unstemmed | Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway |
| title_short | Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway |
| title_sort | engineered panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via jak2 stat3 signaling pathway |
| topic | Rheumatoid arthritis Panax Notoginseng polysaccharide Micelles Macrophage polarization JAK2-STAT3 |
| url | https://doi.org/10.1186/s12951-025-03576-8 |
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