Plant-derived exosome-like nanoparticles and their therapeutic activities

Abstract

Nanotechnologies have been successfully applied to the treatment of various diseases. Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in drug-delivery. PENs are minimally cytotoxic to healthy tissues, with which they show excellent biocompatibility, and are biased towards tumors by targeting specific tissues through special endocytosis mechanisms. Thus, the use of these PENs may expand the scope of drug therapies while reducing the off-target effects. In this review, we summarize the fundamental features and bioactivities of PENs extracted from the grape, grapefruit, ginger, lemon, and broccoli and discuss the applications of these particles as therapeutics and nanocarriers.

Keywords: Drug-delivery systems; Exosomes; Nanocarriers; Plant-derived exosome-like nanoparticles.

Graphical abstract

Fig. 1

Biogenesis and components of MDEs. MDEs are secreted into the extracellular space through an ESCRT-dependent mechanism. The MDEs consist of lipids surrounding proteins, nucleic acids, metabolites, and amino acids, which are responsible for the therapeutic activities.

Fig. 2

A conventional isolation method of MDEs by differential centrifugation. Depending on the original resources of the MDEs, the velocity of centrifugation used may differ. After cell preparation and cell culture, the conditioned medium is collected and purified by differential centrifugation. MDEs pellets are gently dissolved in PBS.

Fig. 3

A schematic illustration of edible-plant–derived exosome-like nanoparticles (PENs). (A) Brief description of the procedure for the isolation of PENs via density-gradient separation. (B) Application of PENs carrying genes, pharmaceuticals, or small molecules. (C) Targeting of mammalian cells by various PENs. (D) Mechanism of PEN-mediated regulation of cellular pathways.

Fig. 4

A schematic illustration of a general method for isolating PENs. Various plants are collected and homogenized. The juice is centrifuged twice at low speed, and the supernatant is sequentially centrifuged at high speeds to isolate nanovesicles containing exosome-like nanoparticles. The pellet and cushion layer are obtained and applied to sucrose gradient fractionation to purify exosome-like nanoparticles via their different buoyant densities.