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

细胞凋亡 活力测定 结直肠癌 MTT法 甲氨蝶呤 癌细胞 药物输送 药理学 化学 体外 癌症研究 材料科学 癌症 分子生物学 医学 纳米技术 生物化学 生物 免疫学 内科学
作者
Zahra Khatibi,Negar Motakef Kazemi,Sepideh Khaleghi
出处
期刊:Journal of Drug Delivery Science and Technology [Elsevier]
卷期号:73: 103441-103441 被引量:21
标识
DOI:10.1016/j.jddst.2022.103441
摘要

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.
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