Abstract
AbstractMicrovesicles (MVs) are heterogeneous membrane‐bound sacs formed by direct plasma membrane budding, that have promising potential for targeted drug delivery and therapy. However, to date, they have limited application to lymph node (LN) targeting due to their large size. Herein, the direct size conversion of erythrocyte‐derived MVs (eMVs) via incubation with an ApoA‐I mimetic peptide (R4F) capable of binding phospholipids is performed. The interaction between the R4F peptide and phospholipid bilayers of eMVs limits the maximum possible length of the lipid‐bound conformation and induces the formation of small‐sized eMVs, which further endows them with SR‐B1 receptor and LN targeting functions. In a lymphadenitis model, dexamethasone (Dex)‐loaded eMVs functionalized with R4F peptide can specifically suppress the macrophage inflammatory response through the NF‐κB and p38 MAPK pathways along with reducing inflammatory cell infiltration to improve lymphadenitis. Moreover, celastrol (Cel)‐loaded eMVs functionalized with R4F peptide can significantly inhibit LN metastasis by selectively killing SR‐B1–overexpressing 4T1 tumor cells and inducing T cell‐mediated systemic antitumor immune responses in LN metastatic model of breast cancer. Thus, small R4F peptide‐decorated eMVs with SR‐B1–targeting ability provide an excellent drug delivery system for the targeted treatment of LN‐associated diseases, opening new frontiers for LN‐targeted drug delivery.
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