Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.

In this work, a bio-metal–organic framework (Bio-MOF) coated with a monodispersed layer of chitosan (CS; CS/Bio-MOF) was synthesized and applied as a pH-responsive and target-selective system for delivery of doxorubicin (DOX) in the treatment of breast cancer. The efficiency of the nanocarrier in loading and releasing DOX was assessed at different pH levels. To monitor the in vitro drug release behavior of the drug-loaded carrier, the carrier was immersed in a phosphate buffered saline solution (PBS, pH 7.4) at 37 °C. According to the observations, the nanocarrier presents a slow and continuous release profile as well as a noticeable drug loading capacity. In addition, the carrier demonstrates a pH-responsive and target-selective behavior by releasing a high amount of DOX at pH 6.8, which is indicative of tumor cells and inflamed tissues and releasing a substantially lower amount of DOX at higher pH values. In addition, the results indicated that pH is effective on DOX uptake by CS/Bio-MOF. A 3.6 mg amount of DOX was loaded into 10 mg of CS/Bio-MOF, resulting in a 21.7% removal at pH 7.4 and 93.0% at pH 6.8. The collapsing and swelling of the CS layers coated on the surface of the Bio-MOFs were found to be responsible for the observed pH dependence of DOX delivery. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the trypan blue test were performed on the MCF-7 (breast cancer) cell line in the presence of the CS/Bio-MOF carrier to confirm its biological compatibility. In addition, Annexin V staining was conducted to evaluate the cytotoxicity of the free and loaded DOX molecules. On the basis of the obtained optical microscopy, MTT assay, fluorescence microscopy, and dyeing results, the CS/Bio-MOF carrier greatly enhances cellular uptake of the drug by the MCF-7 cells and, therefore, apoptosis of the cells due to its biocompatibility and pH-responsive behavior.

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Folic acid amine-functionalized metal−organic framework (FOLA@NH 2 -Eu:TMU-62) with luminescent properties loaded with 5-fluorouracil (5-Fu), as an anticancer medication, was used to construct a new cancer targeted drug delivery system in the present study. The 5-Fu release from this targeted carrier along with MTT assay and trypan blue dye exclusion test results also exhibited pH-controlled characteristics of the given carrier in acidic environments, which is very suitable for targeting solid tumors. Then, the inhibitory action of 5-Fu-loaded FOLA@NH 2 -Eu:TMU-62 for Michigan Cancer Foundation-7 (MCF7) cell migration was explored according to scratch wound healing assays. Based on the results, the FOLA@NH 2 -Eu:TMU-62 carrier was not toxic for MCF-10A normal cells, but it was significantly toxic for MCF-7 breast cancer ones, revealing that the FOLA@NH 2 -Eu:TMU-62 carrier could be utilized in accurate cancer treatments through apoptotic pathways with higher reactive oxygen species compared with 5-Fu alone. This cancer-targeted design of FOLA@NH 2 -Eu:TMU-62 could thus pave the way for synergistic effects of targeting as well as organized release capabilities.

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