Ceria-based nanotheranostic agent for rheumatoid arthritis

Theranostics. 2020 Oct 25;10(26):11863-11880. doi: 10.7150/thno.49069. eCollection 2020.

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.

Keywords: ICG; albumin nanoparticles; imaging; nanoceria; rheumatoid arthritis; theranostics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / pharmacokinetics
  • Arthritis, Experimental / diagnosis
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Cerium / administration & dosage*
  • 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 / administration & dosage*
  • 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

Substances

  • Antirheumatic Agents
  • Coloring Agents
  • Serum Albumin, Bovine
  • Cerium
  • ceric oxide
  • Collagen
  • Freund's Adjuvant
  • Indocyanine Green