Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming—The Potential Role of Ascorbic Acid

Abstract

Citrus fruits are a natural source of ascorbic acid, and exosome-like nanovesicles obtained from these fruits contain measurable levels of ascorbic acid. We tested the ability of grapefruit-derived extracellular vesicles (EVs) to inhibit the growth of human leukemic cells and leukemic patient-derived bone marrow blasts. Transmission electron microscopy and nanoparticle tracking analysis (NTA) showed that the obtained EVs were homogeneous exosomes, defined as exosome-like plant-derived nanovesicles (ELPDNVs). The analysis of their content has shown measurable amounts of several molecules with potent antioxidant activity. ELPDNVs showed a time-dependent antiproliferative effect in both U937 and K562 leukemic cell lines, comparable with the effect of high-dosage ascorbic acid (2 mM). This result was confirmed by a clear decrease in the number of AML blasts induced by ELPDNVs, which did not affect the number of normal cells. ELPDNVs increased the ROS levels in both AML blast cells and U937 without affecting ROS storage in normal cells, and this effect was comparable to ascorbic acid (2 mM). With our study, we propose ELPDNVs from grapefruits as a combination/supporting therapy for human leukemias with the aim to improve the effectiveness of the current therapies.

Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy

“… [ 38 ] Grapefruit Inhibiting the growth of bone marrow progenitor cells derived from leukemia patients. [ 39 ] Quelling the activation of Th17 cells and inducing Treg cell infiltration. [ 40 ] Garlic Inhibiting the activation of the NLRP3 inflammasome.…”

Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study

“…An interesting new approach could be the use of plant-derived exosomes, particularly those derived from organic agriculture, that are entirely free of toxic molecules [39]. Moreover, very recently, the ability of plant-derived exosomes to exert clear antitumor activity has been shown [40]. The ensemble of these reports highly supports the revolutionary role of exosomes in the clinical management of tumor patients.…”

Plant-Derived Exosomes as Novel Nanotherapeutics Contrive Glycolysis Reprogramming-Mediated Angiogenesis for Diabetic Ulcer Healing

“…Nowadays, exosomes derived from medicinal plants that naturally secrete bioactive nanotherapeutics with cell membrane-like structures and stable nanoscale size have been demonstrated for their exceptional biocompatibility, biodegradability, and capability to bypass biological barriers, possessing great potential as therapeutic nanoplatforms for various disease therapies [ 13 – 15 ]. For instance, numerous studies have illustrated that plant-derived exosomes demonstrate remarkable therapeutic effects, including restoring redox balance [ 16 ], anti-leukemic [ 17 ], anti-tumor [ 18 ] properties, and promoting tissue regeneration [ 19 ]. These effects may be attributed to the ability of exosomes to effectively deliver diverse therapeutic payloads, especially small RNAs, to a desired target and influence the diseased cells or tissues [ 20 , 21 ].…”