Route to Rheumatoid Arthritis by Macrophage-Derived Microvesicle-Coated Nanoparticles

The
targeted delivery of therapeutics to sites of rheumatoid arthritis
(RA) has been a long-standing challenge. Inspired by the intrinsic
inflammation-targeting capacity of macrophages, a macrophage-derived
microvesicle (MMV)-coated nanoparticle (MNP) was developed for targeting
RA. The MMV was efficiently produced through a novel method. Cytochalasin
B (CB) was applied to relax the interaction between the cytoskeleton
and membrane of macrophages, thus stimulating MMV secretion. The proteomic
profile of the MMV was analyzed by iTRAQ (isobaric tags for relative
and absolute quantitation). The MMV membrane proteins were similar
to those of macrophages, indicating that the MMV could exhibit bioactivity
similar to that of RA-targeting macrophages. A poly­(lactic-co-glycolic acid) (PLGA) nanoparticle was subsequently coated
with MMV, and the inflammation-mediated targeting capacity of the
MNP was evaluated both in vitro and in vivo. The in vitro binding
of MNP to inflamed HUVECs was significantly stronger than that of
the red blood cell membrane-coated nanoparticle (RNP). Compared with
bare NP and RNP, MNP showed a significantly enhanced targeting effect
in vivo in a collagen-induced arthritis (CIA) mouse model. The targeting
mechanism was subsequently revealed according to the proteomic analysis,
indicating that Mac-1 and CD44 contributed to the outstanding targeting
effect of the MNP. A model drug, tacrolimus, was encapsulated in MNP
(T-RNP) and significantly suppressed the progression of RA in mice.
The present study demonstrates MMV as a promising and rich material,
with which to mimic macrophages, and demonstrates that MNP is an efficient
biomimetic vehicle for RA targeting and treatment.