Peptide targeting improves the delivery and therapeutic index of glucocorticoids to treat rheumatoid arthritis
Copyright © 2024 Elsevier B.V. All rights reserved..
Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by excessive inflammation in the joints. Glucocorticoid drugs are used clinically to manage RA symptoms, while their dosage and duration need to be tightly controlled due to severe adverse effects. Using dexamethasone (DEX) as a model drug, we explored here whether peptide-guided delivery could increase the safety and therapeutic index of glucocorticoids for RA treatment. Using multiple murine RA models such as collagen-induced arthritis (CIA), we found that CRV, a macrophage-targeting peptide, can selectively home to the inflammatory synovium of RA joints upon intravenous injection. The expression of the CRV receptor, retinoid X receptor beta (RXRB), was also elevated in the inflammatory synovium, likely being the basis of CRV targeting. CRV-conjugated DEX increased the accumulation of DEX in the inflamed synovium but not in healthy organs of CIA mice. Therefore, CRV-DEX demonstrated a stronger efficacy to suppress synovial inflammation and alleviate cartilage/bone destruction. Meanwhile, CRV conjugation reduced immune-related adverse effects of DEX even after a long-term use. Last, we found that RXRB expression was significantly elevated in human patient samples, demonstrating the potential of clinical translation. Taken together, we provide a novel, peptide-targeted strategy to improve the therapeutic efficacy and safety of glucocorticoids for RA treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:368 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 368(2024) vom: 01. Apr., Seite 329-343 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Xian [VerfasserIn] |
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| Links: |
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| Themen: |
CRV peptide |
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| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 16.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jconrel.2024.02.040 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369209753 |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by excessive inflammation in the joints. Glucocorticoid drugs are used clinically to manage RA symptoms, while their dosage and duration need to be tightly controlled due to severe adverse effects. Using dexamethasone (DEX) as a model drug, we explored here whether peptide-guided delivery could increase the safety and therapeutic index of glucocorticoids for RA treatment. Using multiple murine RA models such as collagen-induced arthritis (CIA), we found that CRV, a macrophage-targeting peptide, can selectively home to the inflammatory synovium of RA joints upon intravenous injection. The expression of the CRV receptor, retinoid X receptor beta (RXRB), was also elevated in the inflammatory synovium, likely being the basis of CRV targeting. CRV-conjugated DEX increased the accumulation of DEX in the inflamed synovium but not in healthy organs of CIA mice. Therefore, CRV-DEX demonstrated a stronger efficacy to suppress synovial inflammation and alleviate cartilage/bone destruction. Meanwhile, CRV conjugation reduced immune-related adverse effects of DEX even after a long-term use. Last, we found that RXRB expression was significantly elevated in human patient samples, demonstrating the potential of clinical translation. Taken together, we provide a novel, peptide-targeted strategy to improve the therapeutic efficacy and safety of glucocorticoids for RA treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CRV peptide | |
| 650 | 4 | |a Glucocorticoids | |
| 650 | 4 | |a Peptide targeting | |
| 650 | 4 | |a Rheumatoid arthritis | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 700 | 1 | |a Guo, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yiqin |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiangxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Kowalke, Mitchell A |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yue-Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yushuang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Auger, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Binstadt, Bryce A |e verfasserin |4 aut | |
| 700 | 1 | |a Pang, Hong-Bo |e verfasserin |4 aut | |
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