Cell penetrating peptide modified M2 macrophage derived exosomes treat spinal cord injury and rheumatoid arthritis by loading curcumin

Effectively suppressing the hyperactivated inflammatory response is a critical strategy for treating inflammatory diseases, such as spinal cord injury (SCI) and rheumatoid arthritis (RA). Suitable anti-inflammatory drug delivery vehicles need to be continuously explored and discovered to achieve this goal. In this work, we designed M2 macrophage-derived engineered exosomes with a particle size of about 124 nm. Compared with untreated M2 macrophage-derived exosomes, cell-penetrating peptide modified primary M2 macrophage-derived exosomes can be better taken up by target cells, enabling inflammation targeting. The results of experiments in vivo also showed that after cell-penetrating peptide modification, the accumulation of exosomes at the site of inflammation was about 176% of that of unmodified ones. Experiments in SCI or RA mice also showed that primary M2 macrophage exosomes loaded with curcumin penetrating peptide modification had a more prominent ability to inhibit inflammation and improve motor function in inflammation models. Especially in promoting the repolarization of macrophages, in vitro experiments showed that under the action of curcumin loaded and R9 peptide modified M2 macrophage-derived exosomes (Cur@EXs-R9), more than 50% of macrophages were repolarized to M2-type macrophages. In conclusion, the engineered exosomes (Cur@EXs-R9) we designed, provides a new drug delivery carrier for treating inflammatory diseases.