Targeted Combination of Antioxidative and Anti ‐Inflammatory Therapy of Rheumatoid Arthritis using Multifunctional Dendrimer‐Entrapped Gold Nanoparticles as a Platform

A multifunctional dendrimer nanoplatform is developed to have entrapped gold nanoparticles within dendrimer interiors, and covalently linked PEGylated alpha ‐tocopheryl succinate, PEGylated folic acid, and 1,3‐propane sultone on dendrimer peripheries. The designed nanoplatform enables co‐delivery of drug/gene to macrophage cells, effectively scavenging reactive oxygen species and inhibiting tumor necrosis factor‐α expression for combined antiox idative and anti‐inflammatory therapy of rheumatoid arthritis. AbstractAbundant reactive oxygen species and tumor necrosis factor ‐α (TNF‐α) cytokine supply of M1‐type macrophages boost rheumatoid arthritis (RA) pathological process. For efficient RA therapy, here a multifunctional nanoplatform is presented based on generation 5 (G5) poly(amidoamine) dendrimer‐entrapped gold nanoparticles (Au DENPs) to achieve co‐d elivery of antioxidant alpha‐tocopheryl succinate (α‐TOS) and anti‐inflammatory anti‐TNF‐α siRNA to macrophage cells. G5 dendrimers with amine termini are sequentially functionalized with 1,3‐propane sultone (1,3‐PS), α‐TOS through a polyethylene glycol (PEG) spacer, and PEGylated folic acid (FA), and subsequently entrapped with Au NPs. The generated functional Au DENPs exhibit desired cytocompatibility, zwitterion‐rendered antifouling property, and FA‐mediated targeting specificity, enabling serum‐enhanced siRNA delivery to M1‐type macrophage cells. Meanwhile, the a ttached ...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research