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Theranostics ; 10(26): 11863-11880, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204316

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease that affects 1-2% of the human population worldwide, and effective therapies with targeted delivery for local immune suppression have not been described. We address this problem by developing a novel theranostic nanoparticle for RA and assessed its therapeutic and targeting effects under image-guidance. Methods: Albumin-cerium oxide nanoparticles were synthesized by the biomineralization process and further conjugated with near-infrared, indocyanine green (ICG) dye. Enzymatic-like properties and reactive oxygen species (ROS) scavenging activities, as well as the ability to reprogram macrophages, were determined on a monocyte cell line in culture. The therapeutic effect and systemic targeting potential were evaluated in collagen-induced arthritis (CIA) mouse model using optical/optoacoustic tomographic imaging. Results: Small nanotheranostics with narrow size distribution and high colloidal stability were fabricated and displayed high ROS scavenging and enzymatic-like activity, as well as advanced efficacy in a converting pro-inflammatory macrophage phenotype into anti-inflammatory phenotype. When administrated into affected animals, these nanoparticles accumulated in inflamed joints and revealed a therapeutic effect similar to the gold-standard therapy for RA, methotrexate. Conclusions: The inflammation-targeting, inherent contrast and therapeutic activity of this new albumin-cerium oxide nanoparticle may make it a relevant agent for assessing severity in RA, and other inflammatory diseases, and controlling inflammation with image-guidance. The design of these nanotheranostics will enable potential clinical translation as systemic therapy for RA.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Cério/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Antirreumáticos/química , Antirreumáticos/farmacocinética , Artrite Experimental/diagnóstico , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Cério/química , Cério/farmacocinética , Colágeno/administração & dosagem , Colágeno/imunologia , Corantes/administração & dosagem , Corantes/química , Composição de Medicamentos/métodos , Monitoramento de Medicamentos/métodos , Adjuvante de Freund/administração & dosagem , Adjuvante de Freund/imunologia , Meia-Vida , Humanos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/química , Injeções Intra-Articulares , Articulações/diagnóstico por imagem , Articulações/efeitos dos fármacos , Articulações/imunologia , Articulações/patologia , Camundongos , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Células RAW 264.7 , Soroalbumina Bovina/química , Índice de Gravidade de Doença , Células THP-1 , Nanomedicina Teranóstica/métodos , Tomografia/métodos
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