Radicals Scavenging MOFs Enabling Targeting Delivery of siRNA for Rheumatoid Arthritis Therapy

An active targeting nanomedicine based on metal-organic frameworks is synthesized through coordination between tannic acid and Fe3+, loaded with anti-TNF- α siRNA and then modified with bovine serum albumin. The nanosystem can selectively accumulate in inflamed joints, be selectively delivered into M1 macrophages, and exert anti-RA efficacy through the synergistic effects between MOF vector and anti-TNF-α siRNA. AbstractMacrophages play essential roles in the progression of rheumatoid arthritis (RA), which are polarized into the pro-inflammatory M1 phenotype with significant oxidative stress and cytokines excretion. Herein, an active targeting nanomedicine based on metal-organic frameworks (MOFs) to re-educate the diseased macrophages for RA therapy is reported. The MOFs are prepared via coordination between tannic acid (TA) and Fe3+, and anti-TNF- α siRNA is loaded via a simple sonication process, achieving high loading capacity comparable to cationic vectors. The MOFs show excellent biocompatibility, and enable rapid endo/lysosome escape of siRNA via the proton-sponge effect for effective cytokines down-regulation. Importantly, such nanomed icine displays intrinsic radicals scavenging capability to eliminate a broad spectrum of reactive oxygen and nitrogen species (RONS), which in turn repolarizes the M1 macrophages into anti-inflammatory M2 phenotypes for enhanced RA therapy in combination with siRNA. The MOFs are further modified wit h bovine serum albumin (BSA) to all...

Source: Small - June 3, 2022 Category: Nanotechnology Authors: Lina Guo, Shenghui Zhong, Peng Liu, Man Guo, Jinsong Ding, Wenhu Zhou Tags: Research Article Source Type: research