Herbal Medicine-Derived Exosome-Like Nanovesicles: A Rising Star in Cancer Therapy

Abstract

Plant-derived exosome-like nanovesicles (PDNVs) are small nanoscale vesicles containing lipids, RNAs, proteins and some plant natural products secreted by plant cells. Over the last decade, PDNVs have garnered significant interest due to its exceptional therapeutic benefits in the treatment of various diseases. Herbal medicine, as a medicinal plant, plays an important role in the treatment of diseases including cancer. Especially in recent years, the function of herbal medicine derived exosome-like nanovesicles (HMDNVs) in the treatment of cancer has been widely concerned, and has become a research hotspot of nanomedicine. In this review, the biological characteristics, functions and the therapeutic advantages of PDNVs are reviewed, as well as the recent achievements and research progress of HMDNVs in cancer treatment, demonstrating its enormous promise as a cancer therapy, and new insights are provided for future research and development of anti-tumor drugs.

Keywords: cancer treatment; extracellular vesicles; herbal medicine; nanomedicine; plant-derived exosome-like nanovesicles.

Figure 1

Methods of cancer treatment. Chemotherapy and radiotherapy have traditionally been the primary modalities in cancer treatment, however, their non-specific effects on normal cells have prompted the development of more precise and targeted immunotherapies and targeted therapies. In addition, plant natural products have shown promise in cancer treatment due to their anti-cancer properties. To address challenges such as poor solubility and short half-life associated with these natural products, nano delivery methods utilizing metal nanoparticles and artificial liposomes have been developed, but also raises the question of potential toxicity. PDNVs have inherited the anti-cancer activity of natural products combined with plant natural nanovesicles, which have great potential in cancer treatment. The figure was drawn by Figdraw.

Figure 2

Three main types of EVs secreted by eukaryotic cells. Three main types of EVs include apoptotic bodies (1000–5000 nm in diameter) produced by cells in apoptosis as well as microvesicles (100–1000 nm in diameter) and exosomes (30–150 nm in diameter) secreted by cells. The figure was drawn by Figdraw.

Figure 3

Biogenesis and physiological function of PDNVs. a. Fusion of MVB with the plasma membrane results in the release of PDNVs. b. Fusion of MVB with vacuolar or lysosomal membranes results in degradation of the contents. c. PDNVs with large amounts of hydrogen peroxide and callose accumulate around adjacent normal cell to form papillae defensive structures against pathogen invasion. d. PDNVs are taken up by pathogens and silenced its genes critical to pathogenicity. e. PDNVs are taken up by adjacent cells to maintain intercellular communication. f. PDNVs block plasmodesmata for preventing the further penetration of pathogen and the propagation of apoptotic signals. The figure was drawn by Figdraw.

Figure 4

The contents of PDNVs and their functions. The contents of PDNVs primarily consist of lipids, proteins, RNAs, and plant natural products, each serving a crucial function. Lipids are primarily responsible for maintaining the stability and facilitating transport within PDNVs, proteins play a role in immune defense and signal transduction, RNAs mediate cross-kingdom communication and regulate gene expression, and plant natural products contribute to the overall activity of PDNVs. The figure was drawn by Figdraw.

Figure 5

Mechanism of action of PDNVs against tumor cells. a. Promote M2 macrophage polarization are M1 macrophages, changing tumor microenvironment. b. Restrain the growth of the cancer associated fibroblasts, changing tumor microenvironment. c. Promote tumor associated macrophages release CCL5 / CXCL9 in order to promote gathered CD8 + T cells to the tumor. d. Reduce the release of MMP9 in inhibition of cell invasion and migration. e. Activated PI3K/Akt signaling pathway in inhibition of cell proliferation, invasion and migration. f. To block the cell cycle to inhibit cell proliferation. g. Promote the generation of mitochondrial ROS induce mitochondrial damage. h. Induction of mitochondrial membrane potential to reduce. i. Promote the expression of apoptosis factors, reduce the expression of apoptosis inhibiting factor. The figure was drawn by Figdraw.