| Autor: |
Jinteng Li, Feng Ye, Xiaojun Xu, Peitao Xu, Peng Wang, Guan Zheng, Guiwen Ye, Wenhui Yu, Zepeng Su, Jiajie Lin, Yunshu Che, Zhidong Liu, Pei Feng, Qian Cao, Dateng Li, Zhongyu Xie, Yanfeng Wu, Huiyong Shen |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Nanobiotechnology, Vol 21, Iss 1, Pp 1-19 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1477-3155 |
| DOI: |
10.1186/s12951-023-02012-z |
| Popis: |
Abstract Sustained inflammatory invasion leads to joint damage and progressive disability in several autoimmune rheumatic diseases. In recent decades, targeting M1 macrophage polarization has been suggested as a promising therapeutic strategy for autoimmune arthritis. P300/CBP-associated factor (PCAF) is a histone acetyltransferase (HAT) that exhibits a strong positive relationship with the proinflammatory microenvironment. However, whether PCAF mediates M1 macrophage polarization remains poorly studied, and whether targeting PCAF can protect against autoimmune arthritis in vivo remains unclear. Commonly used drugs can cause serious side effects in patients because of their extensive and nonspecific distribution in the human body. One strategy for overcoming this challenge is to develop drug nanocarriers that target the drug to desirable regions and reduce the fraction of drug that reaches undesirable targets. In this study, we demonstrated that PCAF inhibition could effectively inhibit M1 polarization and alleviate arthritis in mice with collagen-induced arthritis (CIA) via synergistic NF-κB and H3K9Ac blockade. We further designed dextran sulfate (DS)-based nanoparticles (DSNPs) carrying garcinol (a PCAF inhibitor) to specifically target M1 macrophages in inflamed joints of the CIA mouse model via SR-A–SR-A ligand interactions. Compared to free garcinol, garcinol-loaded DSNPs selectively targeted M1 macrophages in inflamed joints and significantly improved therapeutic efficacy in vivo. In summary, our study indicates that targeted PCAF inhibition with nanoparticles might be a promising strategy for treating autoimmune arthritis via M1 macrophage polarization inhibition. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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