RESUMO
In the last years, the field of nanomedicine and drug delivery has grown exponentially, providing new platforms to carry therapeutic agents into the target sites. Extracellular vesicles (EVs) are ready-to-use, biocompatible, and non-toxic nanoparticles that are revolutionizing the field of drug delivery. EVs are involved in cell-cell communication and mediate many physiological and pathological processes by transferring their bioactive cargo to target cells. Recently, nanovesicles from plants (PDNVs) are raising the interest of the scientific community due to their high yield and biocompatibility. This study aims to evaluate whether PDNVs may be used as drug delivery systems. We isolated and characterized nanovesicles from tangerine juice (TNVs) that were comparable to mammalian EVs in size and morphology. TNVs carry the traditional EV marker HSP70 and, as demonstrated by metabolomic analysis, contain flavonoids, organic acids, and limonoids. TNVs were loaded with DDHD1-siRNA through electroporation, obtaining a loading efficiency of 13%. We found that the DDHD1-siRNA complex TNVs were able to deliver DDHD1-siRNA to human colorectal cancer cells, inhibiting the target expression by about 60%. This study represents a proof of concept for the use of PDNVs as vehicles of RNA interference (RNAi) toward mammalian cells.
Assuntos
Citrus , Neoplasias Colorretais , Humanos , Animais , RNA Interferente Pequeno/genética , Estudo de Prova de Conceito , Linhagem Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , MamíferosRESUMO
Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti-inflammatory drugs prompt the identification of new therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed-phase high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (RP-HPLC-ESI-Q-TOF-MS). To investigate whether LEVs have a protective role on the inflammatory process, murine and primary human macrophages were pre-treated with LEVs for 24 h and then were stimulated with lipopolysaccharide (LPS). We found that pre-treatment with LEVs decreased gene and protein expression of pro-inflammatory cytokines, such as IL-6, IL1-ß and TNF-α, and reduced the nuclear translocation and phosphorylation of NF-κB in LPS-stimulated murine macrophages. The inhibition of NF-κB activation was associated with the reduction in ERK1-2 phosphorylation. Furthermore, the ability of LEVs to decrease pro-inflammatory cytokines and increase anti-inflammatory molecules was confirmed ex vivo in human primary T lymphocytes. In conclusion, we demonstrated that LEVs exert anti-inflammatory effects both in vitro and ex vivo by inhibiting the ERK1-2/NF-κB signalling pathway.
Assuntos
Citrus , Vesículas Extracelulares , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citrus/metabolismo , Citocinas/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismoRESUMO
The scientific community has become increasingly interested in plant-derived nanoparticles (PDNPs) over the past ten years. Given that they possess all the benefits of a drug carrier, including non-toxicity, low immunogenicity, and a lipid bilayer that protects its content, PDNPs are a viable model for the design of innovative delivery systems. In this review, a summary of the prerequisites for mammalian extracellular vesicles to serve as delivery vehicles will be given. After that, we will concentrate on providing a thorough overview of the studies investigating the interactions of plant-derived nanoparticles with mammalian systems as well as the loading strategies for encapsulating therapeutic molecules. Finally, the existing challenges in establishing PDNPs as reliable biological delivery systems will be emphasized.
RESUMO
Background: There is a correlation between gut microbiota and cognitive function. The mechanisms and pathways explain why the incidence of Alzheimer's disease in subjects undergoing bariatric surgery is lower than in other people with obesity. Methods: In this review article, we aim to discuss the association of obesity, cognitive impairment, and physiological changes after bariatric surgery. Results: Bariatric surgery has a series of physiological benefits which may lead to an improvement in cognitive functions in individuals who are prone to later developing Alzheimer's disease. Also, taxonomical change in the gut microbiome profile provides a healthy condition for living with better levels of cognition without neuropathological damages in older ages. Conclusion: It can be concluded that there is a possible correlation between cognitive dysfunction and increased risk of cognitive dysfunction in people with a BMI higher than 40 kg/m2. Bariatric surgery may increase neurotransmitters and improve the gut bacteria, leading to a significant reduction in the risk of Alzheimer's disease.