Background
Exosomes are a type of membrane vesicles secreted by living cells. Recent studies suggest exosome-like nanovesicles (ELNVs) from fruits and vegetables are involved in tissue renewal process and functional regulation against inflammatory diseases or cancers. However, there are few reports on ELNVs derived from medicinal plants.
Methods
ELNVs derived from
Asparagus cochinchinensis
(Lour.) Merr. (ACNVs) were isolated and characterized. Cytotoxicity, antiproliferative and apoptosis-inducing capacity of ACNVs against hepatoma carcinoma cell were assessed. The endocytosis mechanism of ACNVs was evaluated on Hep G2 cells in the presence of different endocytosis inhibitors. In vivo distribution of ACNVs was detected in healthy and tumor-bearing mice after scavenger receptors (SRs) blockade. PEG engineering of ACNVs was achieved through optimizing the pharmacokinetic profiles. In vivo antitumor activity and toxicity were evaluated in Hep G2 cell xenograft model.
Results
ACNVs were isolated and purified using a differential centrifugation method accompanied by sucrose gradient ultracentrifugation. The optimized ACNVs had an average size of about 119 nm and showed a typical cup-shaped nanostructure containing lipids, proteins, and RNAs. ACNVs were found to possess specific antitumor cell proliferation activity associated with an apoptosis-inducing pathway. ACNVs could be internalized into tumor cells mainly via phagocytosis, but they were quickly cleared once entering the blood. Blocking the SRs or PEGylation decoration prolonged the blood circulation time and increased the accumulation of ACNVs in tumor sites. In vivo antitumor results showed that PEGylated ACNVs could significantly inhibit tumor growth without side effects.
Conclusion
This study provides a promising functional nano platform derived from edible
Asparagus cochinchinensis
that can be used in antitumor therapy with negligible side effects.
Kidney stones, represented by the calcium oxalate (CaOx)
type,
are highly prevalent and recrudescent. Cumulative evidence shows regular
consumption of lemonade intervenes with stone development. However,
the detailed mechanism remains obscure. Here, extracellular vesicle-like
nanoparticles (LEVNs) isolated from lemonade are demonstrated to traffick
from the gut to the kidney, primarily enriched in tubule cells. Oral
administration of LEVNs significantly alleviates the progression of
kidney stones in rats. Mechanistically, in addition to altering the
crystallization of CaOx toward a less stable subtype, LEVNs suppress
the CaOx-induced endoplasmic reticulum stress response of tubule cells,
as indicated by homeostasis of specific signaling molecules and restoration
of subcellular function, thus indirectly inhibiting stone formation.
To exercise this regulation, endocytosed LEVNs traffick along the
microtubules throughout the cytoplasm and are eventually recruited
into lysosomes. In conclusion, this study reveals a LEVNs-mediated
mechanism against renal calculi and provides positive evidence for
consumption of lemonade preventing stone formation.
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