Engineered Plant-Derived Nanovesicles Facilitate Tumor Therapy: Natural Bioactivity Plus Drug Controlled Release Platform

Abstract

Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs' natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.

Keywords: cancer therapy; drug delivery platform; engineered EVs; natural bioactivity; plant-derived nanovesicles; targeted precision therapy.

Graphical abstract

Figure 1

Natural anti-tumor bioactivities of PDNVs. (Grey areas represent untreated tumor tissue, while pink areas represent PDNV-treated tumor tissue).

Figure 2

The natural anti-tumor bioactivity of PDNVs.

Figure 3

Engineered PDNVs as ideal antitumor drug delivery systems.

Figure 4

The schematic of engineered grapefruit-derived NVs as biomimetic drug delivery tools. (a) cRGD and ADH-DOX were modified on heparin and self-assembled into PH-sensitive heparin-modified nanovesicles (DNs). DNs were assembled with extracellular vesicles purified from grapefruit to synthesize biomimetic extracellular vesicles (EV-DNs). (b) The process and situation of endocytosis of EV-DNs in cells.

Figure 5

Engineered PDNVs targeted drug delivery platform. EGFR ligand-modified kiwifruit-derived extracellular vesicles are used as a siSTAT3 delivery platform for the treatment of cancer.