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

Abstract

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.

Leveraging Electrostatic Interactions for Drug Delivery to the Joint

“…Although active targeting modalities such as tuftsin peptides, 120 IL-1Ra, 121 vasoactive intestinal peptides, 122 avb3-targeted RGD, 123,124 folic acid, [125][126][127][128] or macrophagederived microvesicle proteins 129 have been used in various investigations to target cells in the arthritic synovium, there are minimal instances of electrostatic interactions being leveraged for targeting. However, electric charge has been manipulated in other cases to determine preferential targeting of key immune cells that are part of the arthritic synovium, such as phagocytic macrophages.…”

Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy

“…Recruited by inflammatory chemokines to the site of inflammation, macrophages affect the endothelium or pannus of inflammatory vessels by interacting with specific ligands and become "resident" [20,22]. Recently, macrophage membranes were successfully applied to biomimetic delivery systems development to target tumors or inflammatory sites [23][24][25]. Moreover, some reports suggest that macrophages are involved in the early stages of diffusion, significantly impacting long-term metastatic development, which occurs during late-stage tumor progression [26][27][28].…”

Recent Advances of Cell Membrane‐Coated Nanomaterials for Biomedical Applications

“…Cell membrane-coated drug-loaded nanomaterials Good biocompatibility, high drug loading capacity [19][20][21][22] Cell membrane-coated drug-self-assembly nanomaterials [25] Template Cell membrane-coated nanogels Guiding the core formation [27] Nanoreactor Cell membrane-coated a single natural enzyme Improving the stability of enzymes or nanoenzymes in circulation [28,29] Cell membrane-coated a single nanozyme [30] Cell membrane-coated multiple natural enzymes [31,32] Cell membrane-coated multiple nanozymes [33] Cellular communication Circulation Cell membrane-camouflaged polymeric nanomaterials [38,39,43,45] Cell Neutrophil membrane-coated nanomaterials Protection of neutrophils [65] Bacteria membrane-cloaked nanomaterials Protection of body from bacteria adhesion [68] T cell membrane-coated nanomaterials Protection of T cells [69] Targeting Stem cell membrane-coated nanomaterials Enhancing tumor targeting ability [74][75][76][77] Leukocyte membrane-coated nanomaterials [78][79][80][81][82][83][84][85][86][87] Platelet membrane-coated nanomaterials [91,[93][94][95][96][97][98] Tumor cell membrane-coated nanomaterials Homologous targeting ability…”