Ceria-based nanotheranostic agent for rheumatoid arthritis

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.

Recent Advancements in Serum Albumin-Based Nanovehicles Toward Potential Cancer Diagnosis and Therapy

“… Park et al (2021) have designed the PEGylated nanoparticle albumin-bound steroidal ginsenoside to alleviate SARS-CoV-2-mediated hyper-inflammatory responses and demonstrated its potential applications in the treatment of symptoms including coagulation and cytokine storm in severe SARS-CoV-2 patients. Kalashnikova et al (2020) have synthesized the albumin-cerium oxide nanoparticles with indocyanine green (ICG) dye conjugation, which were proven to be accumulated in inflamed joints and showed a similar therapeutic effect to that of methotrexate against rheumatoid arthritis. Amphotericin B (AmB) is a potent fungicide that can bind to albumin in vivo to form a nanocomplex smaller than 10 nm, which is easy to accumulate in the kidneys, and then interacts with cholesterol on renal epithelial cells, eventually leading to the nephrotoxicity ( Hamill, 2013 ; Tang et al, 2015 ; Gurudevan et al, 2018 ).…”

Biocatalytic and Antioxidant Nanostructures for ROS Scavenging and Biotherapeutics

“…[ 69 ] Similarly, cerium oxide NPs (nanoceria) are also potent inhibitors of free radicals due to valence state recycling. [ 70 ] Generally, biocatalytic nanostructures possess the activity center of natural antioxidant enzymes or abundant redox potentials as strong electron transporters, making them scavenge ROS efficiently.…”

Biomimetic and Bioinspired Intervention Strategies for the Treatment of Rheumatoid Arthritis

“…incorporated nanoceria into a SPARC‐specific HSA system to deliver antioxidant and enzymatic properties and facilitate RA therapy by improving hypoxia, ROS scavenging, and shifting M1 macrophages to M2 polarization. [ 138 ] All of these changes are aimed at increasing specific retention and circulation retention in RA, which in turn would significantly improve the therapeutic effect.…”