Abstract
In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and −45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3, NF-1, PDL-1, and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.
Highlights
Vinblastine (VBL) is a natural alkaloid extracted from the Vinca rosea Linn plant
We found that low expression levels of the caspase-3 and NF-1 genes were visibly reduced in cancerous cells cancerous cells treated with folic acid (FA)-DEX-VBL-superparamagnetic iron oxide (SPION) compared with void VBL and FA-DEX-SPION, treated with FA-DEX-VBL-SPION compared with void VBL and FA-DEX-SPION, which suggests that which suggests that the drug was successfully delivered to the site of action of the cancerous cells
VBL sulfate, DEX (15 kDa), ferric chloride hexahydrate dimethyl sulfoxide (DMSO), FeCl3 ·6H2 O, ferrous chloride tetrahydrate (FeCl2 ·4H2 O), the MTT agent, NH4 OH (25% of ammonia), and FA were purchased from Merck (Darmstadt, Germany)
Summary
Vinblastine (VBL) is a natural alkaloid extracted from the Vinca rosea Linn plant. VBL binds to tubulin and inhibits the formation of microtubules, causing disruption of the assembly of mitoticMolecules 2020, 25, 4721; doi:10.3390/molecules25204721 www.mdpi.com/journal/moleculesBiology 2020, 9, x FOR PEER REVIEWVinblastine (VBL) is a natural alkaloid extracted from the Vinca rosea Linn plant. VBL binds to tubulin and inhibits the formation of microtubules, causing disruption of the assembly of mitotic. VBL binds to tubulin and inhibits the formation of microtubules, causing disruption of the assembly of mitotic spindles thethe arrest of tumor cellscells in the of theofcell. VBL, is which is marketed the Velban name, among others, is aothers, chemotherapy drug that is usually used combination under thebrand. Among is a chemotherapy drug that is in usually used in with other drugs treat drugs different typesdifferent of cancer, including breast cancer,breast. Hodgkin’s lymphoma, combination withtoother to treat types of cancer, including cancer, Hodgkin’s brain cancer, brain prostate cancer, and testicular cancer [2,3,4,5]. Its cytotoxicity nonspecific lymphoma, cancer, prostate cancer, and testicular cancer [2,3,4,5].
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