Inflammation-homing “living drug depot” for efficient arthritis treatment

Delivering therapeutic agents efficiently to inflamed joints remains an intractable problem in rheumatoid arthritis (RA) treatment due to the complicated physiological barriers. Circulating monocytes could selectively migrate to inflamed sites and differentiate into resident macrophages to aggravate RA. Therefore, a drug carrier that can be specifically internalized by circulating monocytes and switch monocytes into anti-inflammatory phenotype when reaching inflamed sites, might bypass the in vivo physiological barriers and achieve efficient RA therapy. Herein, we design a dextran sulfate (DS) functionalized nanoparticle (ZDNP) to selectively deliver anti-inflammatory agent dexamethasone (Dex) to circulating monocytes via the scavenger receptors on monocytes. Monocytes engulfing drug-loaded ZDNP could subsequently home to arthritic joints and act as a “living drug depot” to combat RA. Results revealed that ZDNP could be preferentially internalized by circulating monocytes when intravenously administrated in vivo. In a rat arthritic model, we found that circulating monocytes remarkably facilitated drug distribution and retention in inflamed joints. Moreover, monocytes engulfing drug-loaded nanoparticles exhibited favorable anti-inflammatory ability and M2-biased differentiation. Our work offers a facile approach to achieve site-directed anti-inflammatory therapy by taking advantage of the inflammation-homing ability of circulating monocytes.