Retinoic Acid-Loaded Poly(lactic-co-glycolic acid) Nanoparticle Formulation of ApoB-100-Derived Peptide 210 Attenuates Atherosclerosis

Abstract

We developed a vaccine formulation containing ApoB derived P210 peptides as autoantigens, retinoic acid (RA) as an immune enhancer, both of which were delivered using PLGA nanoparticles. The formula was used to induce an immune response in 12-week-old male Apoe–/– mice with pre-existing atherosclerotic lesions. The nanotechnology platform PRINT® was used to fabricate PLGA nanoparticles that encapsulated RA inside and adsorbed the P210 onto the particle surface. In this study, we demonstrated that immunization of Apoe–/– mice with the formulation was able to considerably attenuate atherosclerotic lesions, accompanied by increased P210 specific IgM and another oxidized lipid derived autoantigen, M2AA, specific IgG autoantibodies, and decreased the inflammatory response, as compared to the P210 group with Freund's adjuvant. Our formulation represents an exciting technology to enhance the efficacy of the P210 vaccine.

Potential Therapeutic Effect of All-Trans Retinoic Acid on Atherosclerosis

“…The current dose of ATRA in clinical use is 0.1–1 μM, and high doses of ATRA may bring serious adverse reactions [ 140 ]. With the development of nanotechnology, the targeted delivery of ATRA in the treatment of atherosclerosis has greater benefits and fewer adverse reactions [ 141 ]. The pathological process of atherosclerosis is complicated.…”

Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance

“…Similarly to murine mucosal CD103+ DCs ( 167 ), human moDCs raised with atRA, induce the development of IL-10 producing Tr1 in co-culture ( 41 ). Building on the anti-inflammatory potential of atRA, the compound was recently incorporated in PLGA particles together with atherosclerosis autoantigen and improved atherosclerotic lesions in vivo ( 168 ). In a further recent study, atRA was encapsulated together with another anti-inflammatory adjuvant, triptolide, in galactose-containing nanoparticles ( 78 ).…”