In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy
Abstract Rheumatoid arthritis (RA) is an autoimmune disorder characterized by painful swelling and inflammation, arising from the immune system attacking on healthy cells. However, arthritic sites often experience increased lymph flow, hastening drug clearance and potentially reducing treatment effe...
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BMC
2024-12-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-03061-8 |
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| author | Xianyan Qin Luhan Zhang Yang-Bao Miao Linxi Jiang Liang Zou Qin Wang Yi Shi |
| author_facet | Xianyan Qin Luhan Zhang Yang-Bao Miao Linxi Jiang Liang Zou Qin Wang Yi Shi |
| author_sort | Xianyan Qin |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA) is an autoimmune disorder characterized by painful swelling and inflammation, arising from the immune system attacking on healthy cells. However, arthritic sites often experience increased lymph flow, hastening drug clearance and potentially reducing treatment effectiveness. To address this challenge, an in situ size amplification has been proposed to reduce lymphatic clearance and thereby enhance arthritis therapy. This system has been developed based on a conjugate of dexamethasone (Dex) and polysialic acid (PSA), linked via an acid-sensitive linker, supplemented with bis-5-hydroxytryptamine (Bis-5HT) on the PSA backbone. Under physiological conditions, the system autonomously assembles into stable nanoparticles (PD5NPs), facilitating prolonged circulation and targeted delivery to inflamed joints. Upon arrival at arthritic joints, Bis-5HT reacts to elevated myeloperoxidase (MPO) levels and oxidative stress, prompting particle aggregation and in-situ size amplification. This in situ size amplification nanocarrier effectively reduces lymphatic clearance and serves as reservoirs for sustained Dex release in acidic pH environments within arthritic sites, thus continuously alleviating RA symptoms. Moreover, investigation on the underlying mechanism elucidates how the in situ size amplification nanocarrier influences the transportation of PD5NPs from inflamed joints to lymphatic vessels. Our study offers valuable insights for optimizing nanomedicine performance in vivo and augmenting therapeutic efficacy. Graphical Abstract |
| format | Article |
| id | doaj-art-80c01a876c2f4862b0214f7124bf50d9 |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-80c01a876c2f4862b0214f7124bf50d92025-08-20T02:39:41ZengBMCJournal of Nanobiotechnology1477-31552024-12-0122111610.1186/s12951-024-03061-8In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapyXianyan Qin0Luhan Zhang1Yang-Bao Miao2Linxi Jiang3Liang Zou4Qin Wang5Yi Shi6Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaSchool of Food and Biological Engineering, Chengdu UniversityInstitute of Biomedical Engineering, College of Medicine, Southwest Jiaotong UniversitySichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaAbstract Rheumatoid arthritis (RA) is an autoimmune disorder characterized by painful swelling and inflammation, arising from the immune system attacking on healthy cells. However, arthritic sites often experience increased lymph flow, hastening drug clearance and potentially reducing treatment effectiveness. To address this challenge, an in situ size amplification has been proposed to reduce lymphatic clearance and thereby enhance arthritis therapy. This system has been developed based on a conjugate of dexamethasone (Dex) and polysialic acid (PSA), linked via an acid-sensitive linker, supplemented with bis-5-hydroxytryptamine (Bis-5HT) on the PSA backbone. Under physiological conditions, the system autonomously assembles into stable nanoparticles (PD5NPs), facilitating prolonged circulation and targeted delivery to inflamed joints. Upon arrival at arthritic joints, Bis-5HT reacts to elevated myeloperoxidase (MPO) levels and oxidative stress, prompting particle aggregation and in-situ size amplification. This in situ size amplification nanocarrier effectively reduces lymphatic clearance and serves as reservoirs for sustained Dex release in acidic pH environments within arthritic sites, thus continuously alleviating RA symptoms. Moreover, investigation on the underlying mechanism elucidates how the in situ size amplification nanocarrier influences the transportation of PD5NPs from inflamed joints to lymphatic vessels. Our study offers valuable insights for optimizing nanomedicine performance in vivo and augmenting therapeutic efficacy. Graphical Abstracthttps://doi.org/10.1186/s12951-024-03061-8Rheumatoid arthritisNanomedicine deliveryIn situ size amplificationAggregatesLymphatic clearance |
| spellingShingle | Xianyan Qin Luhan Zhang Yang-Bao Miao Linxi Jiang Liang Zou Qin Wang Yi Shi In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy Journal of Nanobiotechnology Rheumatoid arthritis Nanomedicine delivery In situ size amplification Aggregates Lymphatic clearance |
| title | In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy |
| title_full | In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy |
| title_fullStr | In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy |
| title_full_unstemmed | In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy |
| title_short | In situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy |
| title_sort | in situ size amplification strategy reduces lymphatic clearance for enhanced arthritis therapy |
| topic | Rheumatoid arthritis Nanomedicine delivery In situ size amplification Aggregates Lymphatic clearance |
| url | https://doi.org/10.1186/s12951-024-03061-8 |
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