Plant-derived extracellular vesicles as a novel tumor-targeting delivery system for cancer treatment

Abstract

Extracellular vesicles (EVs) are vital mediators of intercellular communication, helping to transfer bioactive molecules to target cells and demonstrating significant potential in antitumor therapy. Currently, EVs are primarily utilized in clinical applications such as biomarker discovery, cell-free therapeutic agents, drug delivery systems, pharmacokinetic studies, and cancer vaccines. Plant-derived EVs (P-EVs) contain a range of lipids, proteins, nucleic acids, and other metabolite cargos, and it is possible to extract them from various plant tissues, including juice, flesh, and roots. These vesicles perform multiple biological functions, including modulating cellular restructuring, enhancing plant immunity, and defending against pathogens. P-EVs have also been investigated in various clinical trials due to their promising therapeutic properties. In the context of precision medicine, selectively inhibiting solid tumor growth while preserving the viability of normal human cells remains a primary objective of cancer therapy. However, the tumor microenvironment (TME) supports tumor progression through the facilitation of immune evasion, supplying nutrients, and promoting invasive growth, metastatic processes, and treatment resistance. Consequently, the development of novel antitumor agents is essential. Owing to their inherent therapeutic properties and potential as treatment vectors, natural P-EVs represent a promising biocompatible platform for targeted solid tumor therapy. These vesicles may contribute to remodeling the TME and enhancing antitumor immunity, offering innovative avenues for cancer treatment and improved human health.

Keywords: antitumor therapy; plant-derived extracellular vesicles; precision medicine; solid tumors; tumor microenvironment.

FIGURE 1

Current status of mammalian-derived EVs and plant-derived EVs. EVs, extracellular vehicles; PA, phosphatidic acid; PE, phosphatidylethanolamine; PC, phosphatidylcholine; SOD, superoxide dismutase; ROS, reactive oxygen; HSP, heat shock protein 70; SAH, S-adenosyl-homocysteinase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; ctDNA, circulating tumor DNA; siRNA, small interfering RNA; miRNA, microRNA; lncRNA, long non-coding RNA; circRNA, circular RNA; sRNAs, this refers to other undiscovered small RNAs.

FIGURE 2

The existing pathways cascade of P-EVs in the TME (partial). TME, tumor microenvironment; CAFs, cancer-associated fibroblasts; Tregs, regulatory T cells; iv, intravenous; 5-Fu, 5-Fluorouracil; cGAS, cyclic GMP-AMP synthase; STING, stimulator of interferon genes; iNOS, inducible nitric oxide synthase; EGF, epidermal growth factor; VEGF, vascular endothelial growth factor; STAT, signal transducer and activator of transcription; CCL5, C-C motif chemokine ligand5; CXCL9, C-X-C motif chemokine ligand9; PD-1 mAb, programmed cell death protein1 monoclonal antibody; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; AKT, protein kinase B; ERK, extracellular signal-regulated kinase; PI3K, phosphatidylinositol 3-kinase; mTOR, mechanistic target of rapamycin; ROS, reactive oxygen; JAK, janus kinase; NLRP3, NOD-like receptor family, pyrin domain containing3.