NaHS@Cy5@MS@SP nanoparticles improve rheumatoid arthritis by inactivating the Hedgehog signaling pathway through sustained and targeted release of H2S into the synovium DOI Creative Commons
Xuexue Zhu,

An‐Jing Xu,

Weiwei Cai

и другие.

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 8, 2025

Aberrant proliferation and inflammation of fibroblast-like synoviocytes (FLSs) significantly contribute to the pathogenesis rheumatoid arthritis (RA). Deficiency hydrogen sulfide (H2S) is a driving force for development RA, short half-life H2S-releasing donor sodium hydrosulfide (NaHS) limits its clinical application in RA therapy. Designing targeted delivery system with slow-release properties FLSs could offer novel strategies treating RA. Herein, we designed strategy achieve slow release H2S synovium, which was accomplished by synthesizing NaHS-CY5@mesoporous silic@LNP peptide Dil (NaHS@Cy5@MS@SP) nanoparticles. Our results demonstrated that NaHS@Cy5@MS@SP effectively targets FLSs, upregulates its-producing enzyme cystathionine-γ-lyase (CSE) joints arthritic mice. Overexpression CSE inhibited proliferation, migration, upon lipopolysaccharide (LPS) exposure, effects were mimicked NaHS@Cy5@MS@SP. In vivo studies showed achieved threefold higher AUCinf than free NaHS, improving bioavailability NaHS. Further, synovial hyperplasia reduced bone cartilage erosion DBA/1J mouse model collagen-induced (CIA), superior RNA sequencing molecular validated inactivated Hedgehog signaling pathway as evidenced reductions protein expression SHH, SMO, GLI1 phosphorylated p38/MAPK. This study highlights promising controlled synoviocytes, offering potential management.

Язык: Английский

NaHS@Cy5@MS@SP nanoparticles improve rheumatoid arthritis by inactivating the Hedgehog signaling pathway through sustained and targeted release of H2S into the synovium DOI Creative Commons
Xuexue Zhu,

An‐Jing Xu,

Weiwei Cai

и другие.

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 8, 2025

Aberrant proliferation and inflammation of fibroblast-like synoviocytes (FLSs) significantly contribute to the pathogenesis rheumatoid arthritis (RA). Deficiency hydrogen sulfide (H2S) is a driving force for development RA, short half-life H2S-releasing donor sodium hydrosulfide (NaHS) limits its clinical application in RA therapy. Designing targeted delivery system with slow-release properties FLSs could offer novel strategies treating RA. Herein, we designed strategy achieve slow release H2S synovium, which was accomplished by synthesizing NaHS-CY5@mesoporous silic@LNP peptide Dil (NaHS@Cy5@MS@SP) nanoparticles. Our results demonstrated that NaHS@Cy5@MS@SP effectively targets FLSs, upregulates its-producing enzyme cystathionine-γ-lyase (CSE) joints arthritic mice. Overexpression CSE inhibited proliferation, migration, upon lipopolysaccharide (LPS) exposure, effects were mimicked NaHS@Cy5@MS@SP. In vivo studies showed achieved threefold higher AUCinf than free NaHS, improving bioavailability NaHS. Further, synovial hyperplasia reduced bone cartilage erosion DBA/1J mouse model collagen-induced (CIA), superior RNA sequencing molecular validated inactivated Hedgehog signaling pathway as evidenced reductions protein expression SHH, SMO, GLI1 phosphorylated p38/MAPK. This study highlights promising controlled synoviocytes, offering potential management.

Язык: Английский

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