چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| یلدا رهبرسعادت | اول |
| ژاله برار | چهارم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | Cancer is a heterogeneous group of diseases and has become a prominent reason of death worldwide. It is a complex pathological disorder characterized by altered gene expression, aberrant genetic mutations and genomic instability (1). Extracellular vesicles (EVs) are lipid bilayer heterogeneous membranous structures and they are usually spherical in shape with the average diameter of 30- 500 nm. They carry different components both on the surface and as cargo. EVs are key mediators of various (patho)physiological procedures. They play a pivotal role in diverse cell-to-cell signaling processes. EVs are employed as delivery vehicles of therapeutic agents, peptides, and nucleic acids. Almost all living organisms secrete EVs such as eukaryotic and prokaryotic cells (2). It has been discovered that various plants can produce EVs that influence neighboring as well as remote cells, thus they are involved in intercellular & interspecies interactions. The content of EVs is different based on the producing cells, so plant-derived extracellular vesicles (PDEVs) content is different from mammalian EVs. The structure of PDEVs protects their content against harsh conditions (RNase and extreme pH). PDEVs possess numerous health-promoting effects including immunomodulatory activity, modulation of gut microbiota, anticancer properties, drug delivery & etc. These structures can pass through blood-brain-barrier however they cannot pass the placental barrier, which reveals that PDEVs may be potentially beneficial vehicles for drug delivery during pregnancy (3,4). PDEVs entrance into the cancerous cells leads to regulation of gene expression to lessen the phenotypes associated with cancer. For example, Raimondo & colleagues extracted EVs fromlemon juice. They investigated LDEVs role in the treatment of chronic myeloid leukemia (CML). Reduced growth of LAMA84 (chronic myeloid leukemia) cells was observed. To confirm the effects of EVs specificity on cancer cells, LDEVs were also treated with normal cell line. LDEVs did not affect normal cells growth. Moreover, gene expression analysis indicated the involvement of apoptosis process. Also, the expression of pro-angiogenic genes were increased in LAMA84 cell line after LDEV treatment. Additionally, they studied the potential LDEVs in reducing tumor growth in vivo. The intraperitoneal injection of LDEVs into mice bearing CML xenograft tumors, indicated that elevated pro-apoptotic and decreased antiapoptotic as well as pro-angiogenic factors (VEGF-A, IL6, and IL8) levels (5). In another in vitro study, the anticancer activities of LDEVs on three gastric cancer cell lines (AGS, BGC- 823, and SGC-7901) as well as SGC-7901 three-dimensional (3D) spheroid culture were assessed. The results demonstrated LDEVs could be efficiently taken up by 3D spheroid cultured cells. LDEVs caused the gastric cancer cell cycle S-phase arrest and induced cell apoptosis (6). Recently, the anticancer effect of garlic derived EVs (GEVs) was investigated on two cancer cell lines A498 (renal cancerous cells) & A549 (lung cancer) and one normal Human Dermal Fibroblasts cell line, HDF. The GEVs treatment significantly reduced the viability of cancer cells, however, it did not cause a cytotoxic effect on the normal cell line. The reasons for decreased cell proliferation among cancer cells in response to GEVs treatment was the S phase cell cycle arrest (7). Nowadays, the formation of nontoxic natural nano-vectors from PDEVs, is considered as an alternative approach in nanomedicine and drug delivery. In addition, owing to their small size, PDEVs can successfully deliver therapeutic agents. Recently, the anticancer activity of EVs isolated from cabbage and red cabbage were evaluated on SW480 colon cancer cells. Both Cabex and Rabex demonstrated efficient Dox loading and suppression of cancer cell proliferation. It has been shown that Dox loaded onto Cabex and Rabex successfully delivered to cancer cells, entered the nucleus and exert its cytotoxic effects (8). In an investigation, the intranasal delivery of miR17-carrying grape fruit derived EVs coated with folic acid (FAGEVs), which exclusively targeted the brain tumor GL-26 cells in mouse model, showed no observable side effects. Addition of folic acid results in enhanced targeting and selective delivery to a folate receptor-positive GL-26 brain tumor. miR17-loaded GEVs inhibited the growth of brain tumor (9). In another research, folic acid coated ginger-derived EVs (GDEVs) could efficiently take up by Colon-26 cells. Furthermore, drug loading efficiency and drugrelease of GDEVs loaded Doxorubicin (Dox) were evaluated. GDEVs loaded with Dox demonstrated high efficiency & and interestingly diffused Dox more rapidly than the commercially available liposomes. Additionally, GDEVs-Dox induced apoptosis in Colon-26 tumor xenograft mouse model (10). In an animal study, intravenous (IV) injection of folic acid coated grapefruit-derived EVs (GEVs-FA) was detectable even after 48h of circulation, giving them a greater opportunity to penetrate tumors. The GEVs-FA did not pass the placental barrier, which reveals that they could be potentially beneficial vehicles for drug delivery during pregnancy. Additionally, the therapeutic effects GEVs following the co-delivery of folic acid and PTX (an anticancer compound), were evaluated in comparison to the administration of each drug alone. Bio-distribution findings in mice model bearing colon tumor, treated with GEVs, PTX, and GEVs-FA-PTX, indicated that that free GEVs and PTX mostly targeted liver and spleen, whereas GEVs-FA-PTX mainly targeted the tumors and markedly reduced tumor growth of colon cancer xenograft mouse models (11). Two PDEVs have just been registered for clinical trials. In order to alleviating oral mucositis associated with chemo-radiation following head & neck cancer, a randomized clinical trial was designed. The grape-derived EVs should have been administered for 60 patients (20 to 85 Years) diagnosed with head and neck cancer. But the patients could not be recruited (12). Another randomize clinical trial (NCT01294072) was designed based on PDEV-curcumin delivery to colon tumors and normal colon tissue. The PDEV-curcumin should have been administered for 35 patients (20 Years and older). However, this has not yet reached the recruitment phase. |
| کلمات کلیدی |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| Yalda RAHBAR SAADAT.pdf | 1404/07/15 | 261300 | دانلود |
| IOEC.21.37_Yalda RAHBAR SAADAT.pdf | 1404/07/15 | 363306 | دانلود |
| Rahbar Saadat.pdf | 1404/07/15 | 232776 | دانلود |
