Targeted and biocompatible NMOF as efficient nanocomposite for delivery of methotrexate to colon cancer cells

Abstract

Colon cancer has the highest death rate all around the world and conventional therapeutic approaches are not already terminated the colon cancer prevalence. Thus, a novel folic acid (FA)-chitosan (CS)-coated nanoscale metal-organic frameworks (NMOFs) was developed in this study for active delivery of methotrexate (MTX) to colon cancer cells. After qualification and quantification of synthesized MOF-CS-FA-MTX nanocomposite via FT-IR, XRD, DLS, SEM, and TEM devices and verifying the nano-size diameter of the nanocomposite, drug loading capacity (78%) and drug release manner (10% ˃ within first 5h) were measured in vitro. MTX release was indicated pH sensitivity and its release was about 10 folds higher in acidic pH than normal pH within the first 5 h. The MTT assay was indicated less than 5% cell viability in HCT116 cells after treatment with a 2.5 ng/mL concentration of MOF-CS-FA-MTX after 48 h of treatment. The gene expression study was exhibited a 6-fold increase in BAX and a 2-fold decline in Bcl2 genes expression, and BECLIN1 and ATG5 autophagy genes were also shown a nearly 5-fold rise in their expression after treatment with 5 ng/mL MOF-CS-FA-MTX. The cell cycle arrest (15.49% apoptosis) and apoptosis (20% apoptosis) assays during 5 h were potentially approved for the cancer cell inhibition ability of MOF-CS-FA-MTX. These outputs have been presenting a remarkable potency of NMOF-CS-FA-MTX in suppressing colon cancer cells.