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.
Recently, photothermal therapy (PTT) that utilizes photothermal conversion (PTC) agents to ablate cancer under near-infrared (NIR) irradiation has attracted a growing amount of attention because of its excellent therapeutic efficacy and improved target selectivity. Therefore, exploring novel PTC agents with an outstanding photothermal effect is a current research focus. Herein, we reported a polydopamine-coated magnetic composite particle with an enhanced PTC effect, which was synthesized simply through coating polydopamine (PDA) on the surface of magnetic Fe3O4 particles. Compared with magnetic Fe3O4 particles and PDA nanospheres, the core-shell nanomaterials exhibited an increased NIR absorption, and thus, an enhanced photothermal effect was obtained. We demonstrated the in vitro and in vivo effects of the photothermal therapy using our composite particles and their ability as a contrast agent in the T2-weighted magnetic resonance imaging. These results indicated that the multifunctional composite particles with enhanced photothermal effect are superior to magnetic Fe3O4 particles and PDA nanospheres alone.
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