1. Ceria-based nanotheranostic agent for rheumatoid arthritis.
- Author
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Kalashnikova I, Chung SJ, Nafiujjaman M, Hill ML, Siziba ME, Contag CH, and Kim T
- Subjects
- Animals, Antirheumatic Agents chemistry, Antirheumatic Agents pharmacokinetics, Arthritis, Experimental diagnosis, Arthritis, Experimental immunology, Arthritis, Experimental pathology, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid immunology, Arthritis, Rheumatoid pathology, Cerium chemistry, Cerium pharmacokinetics, Collagen administration & dosage, Collagen immunology, Coloring Agents administration & dosage, Coloring Agents chemistry, Drug Compounding methods, Drug Monitoring methods, Freund's Adjuvant administration & dosage, Freund's Adjuvant immunology, Half-Life, Humans, Indocyanine Green administration & dosage, Indocyanine Green chemistry, Injections, Intra-Articular, Joints diagnostic imaging, Joints drug effects, Joints immunology, Joints pathology, Mice, Nanoparticles chemistry, Photoacoustic Techniques methods, RAW 264.7 Cells, Serum Albumin, Bovine chemistry, Severity of Illness Index, THP-1 Cells, Theranostic Nanomedicine methods, Tomography methods, Antirheumatic Agents administration & dosage, Arthritis, Experimental drug therapy, Arthritis, Rheumatoid drug therapy, Cerium administration & dosage, Nanoparticles administration & dosage
- Abstract
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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2020
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