Prostate, ovary, breast, pancreas, etc. and in vivo xenograft models [134]. Curcumin, essentially the most bio-active polyphenol from turmeric, presented a five-fold larger concentration and practically four-fold higher stability than absolutely free curcumin when packaged with EL-4 (murine lymphoma) cell-derived exosomes via mixing and gradient centrifugation. These curcumin-filled exosomes (Exo-Cur) showed nearly five- to ten-fold larger curcumin content for any longer period in peripheral blood upon oral administration when studied in murine-xenograft model. Consequently, a heightened anti-inflammatory and anti-cancer impact was also obtained with Exo-Cur in different cancer cell lines or tissues for example the breast, lung, and cervix [148]. In a different study, precisely the same Exo-Cur markedly retarded the tumor development of GL26-xenograft murine brain tumor model [141]. Chemopreventive phytochemicals which include withaferin A or anthocyanidins had been packaged inside cow milk-derived exosome via mixing and centrifugation. They showed significant toxicity in lung cancer (A549 and H1299) cells and in breast cancer (MDA-MB231 and T47D) cells, as evidenced from a much-reduced IC50 value from the encapsulated from than the cost-free kind of those chemopreventive agents. This exosomal formulation has even minimized NF-B-mediated inflammatory stress. Nevertheless, all of those anti-cancer effects of loaded exosomes are dose-time dependent and very cancer-specific, leaving the normal healthy cells (bronchial BEAS-2B) unaffected. The A549-xenografted animal model has also shown tumor development retardation and volume-shrinkage upon oral treatment from the abovementioned exosomal formulation [127]. Honokiol, an anti-tumor phytochemical from magnolia when packed in MSC-derived exosomes by sonication proved to be much more effective than the free compound in various cancer cell lines which include pancreatic (MiaPaCa and Colo357), breast (MDA-MB-231), ovarian (SK-OV-3), colon (HT-29), and prostate (LNCaP) cells. Improved therapeutic possible with regards to the upregulation of cell-cycle Glutarylcarnitine Protocol arrest and apoptotic response, plus the downregulation of survival-associated aspects and clonogenic properties was accomplished owing towards the improved cellular concentration of honokiol in exosome-encapsulated cases over the administration of no cost honokiol [135]. Celastrol, a triterpenoid phytochemical packaged in milk-derived exosome brought on a considerable dose-time-dependent development inhibition when compared with celastrol alone in NSCLC (A549 and H1299) cell lines by decreasing NF-B-mediated inflammation and by increasing endoplasmic reticulum-stress mediated apoptosis. The superior anti-tumor impact of this celastrol-loaded exosome was also proved inside the lung cancer xenograft model, where no undesirable systemic toxicity was located to be an added advantage of this exosome formulation than the nonspecific absolutely free celastrol [140].Bioengineering 2021, 8,22 of5.four.two. Other Small Molecules Porphyrine, a photo-sensitive synthetic drug, showed remarkable cellular retention compared with all the only drug or free exosome when integrated with MDA-MB-231-derived TEX by way of various strategies for instance passive mixing or active electroporation/saponin-assisted incubation/extrusion/dialysis. On reintroduction into that breast cancer cell line, it resulted in Cysteinylglycine Epigenetics substantial cancer cytotoxicity in presence of light [139]. 4T1-derived TEX was co-incubated with sinoporphyrin sodium to kind a nano-sized ultrasonic sound sensitizer, which had both therapeutic and imaging properties. This f.