Decoy Oligodeoxynucleotides, Polysaccharides, and Targeted Peptide-Functionalized Gold Nanorods for the Combined Treatment of Rheumatoid Arthritis.

Zhang, Nan; Zhang, Shasha; Xu, Chunyu; Fu, Lingling; Liu, Tuanbing; Zhao, Yongxing · Adv Healthc Mater · 2018

basic_science · Level V

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Abstract

Autoimmune diseases like rheumatoid arthritis (RA) possess complicated pathogenesis. Therefore, RA is hard to treat by monotherapies in clinical setting. All-in-one treatments that target inflamed joints and act efficiently are highly needed. Gold compounds are old anti-RA therapies and are fabricated into gold nanorods (GNRs) that serve as anti-RA therapeutics as well as nanocarriers for anti-inflammatory nucleic acid drug-NF-κB-decoy oligodeoxynucleotides (dODNs). A targeted peptide to vascular cell adhesion molecule-1 (VCAM-1) (P<sub>VCAM-1</sub> ) is modified onto the GNRs to facilitate enhanced accumulation of GNRs in inflamed tissues and enhanced cellular uptake of GNRs by inflamed cells. dODNs loaded and P<sub>VCAM-1</sub> modified GNRs (GNRs-dODN-P<sub>VCAM-1</sub> ) are covered by polysialic acid (PSA) to protect GNRs-dODN-P<sub>VCAM-1</sub> in vivo. Simultaneous GNRs, dODN, and thermotherapy show synergic effect on the reduction of TNF-α and IL-6 in inflamed macrophages and blood vessel cells. The simultaneous triple therapy (GNRs-dODN-PSA-P<sub>VCAM-1</sub> +laser) demonstrates excellent anti-inflammatory efficacy in vitro and in vivo.