| Autor: |
Dongyang Zhou, Yan Wei, Shihao Sheng, Miaomiao Wang, Jiajing Lv, Bowen Zhao, Xiao Chen, Ke Xu, Long Bai, Yan Wu, Peiran Song, Liehu Cao, Fengjin Zhou, Hao Zhang, Zhongmin Shi, Jiacan Su |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Bioactive Materials, Vol 37, Iss , Pp 378-392 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2452-199X |
| DOI: |
10.1016/j.bioactmat.2024.04.010 |
| Popis: |
Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvβ3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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