Surface‐Functionalizable Plant‐Derived Extracellular Vesicles for Targeted Drug Delivery Carrier Using Grapefruit

Abstract

Recently, membrane‐modified mammalian exosomes have been considered strong candidates for targeted drug delivery carriers because of their biocompatibility, biodistribution, and low immune response. However, the widespread utilization of exosomes still requires overcoming several challenging issues, including low stability, high production cost, and low mass productivity. Therefore, artificial extracellular vesicles (EVs) derived from cell membranes or liposomes containing various lipids have been suggested. However, only a few meet the demands of cost‐effective mass production and durability of EVs. Therefore, this study investigates the feasibility of replacing mammalian cell exosomes and liposomes with plant‐derived extracellular vesicles (pEVs) as targeted drug delivery carriers. They are characterized by nontoxicity, high stability, and high yield. Adding a functionalizable lipid moiety with a maleimide group at the membrane of grapefruit‐derived pEVs imparts targeting ability. The targeting function can be easily enhanced by attaching an aptamer using click chemistry. Indeed, treatment of brain cells with pEV‐aptamers (hCMEC/D3 and U87MG) confirms that aptamer functionalization of pEV enhanced selective cellular uptake. Functionalization of the pEV membrane using aptamer is expected to be effective in providing low‐cost and mass‐producible targeted drug delivery carriers with similar efficacy as mammalian exosomes or liposomes.

Kaempferia parviflora Extracellular Vesicle Loaded with Clarithromycin for the Treatment of Helicobacter pylori Infection

“…39 A similar size increase was also observed when doxorubicin was loaded into grapefruit PDEVs. 40 EVs generally exhibit a negative surface charge, contributed by their structural components (ie, phospholipids and glycans) and surface-associated biomolecules such as nucleic acids. 41 Although, CLA having a positive charge at pH 7, loading CLA into KPEVs did not change their negative surface charge.…”

Recent advances in therapeutic engineered extracellular vesicles

“…50 Moon et al engineered EVs derived from grapefruits with a targeted aptamer. 91 These engineered EVs could have 3 times higher affinity towards blood–brain barrier endothelial cells, compared with unmodified EVs, indicating their potential in targeting brain tumors.…”