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

被引:31
作者
Khatibi, Zahra [1 ]
Kazemi, Negar Motakef [2 ]
Khaleghi, Sepideh [1 ,3 ]
机构
[1] Islamic Azad Univ, Fac Adv Sci & Technol, Dept Biotechnol, Tehran Med Sci, Tehran, Iran
[2] Islamic Azad Univ, Fac Adv Sci & Technol, Dept Med Nanotechnol, Tehran Med Sci, Tehran, Iran
[3] Islamic Azad Univ, Fac Adv Sci & Technol, Tehran Med Sci, Tehran 1916893813, Iran
关键词
Zinc-based NMOF; Folic acid-chitosan; Methotrexate; Controlled drug release; Colon cancer therapy; METAL-ORGANIC FRAMEWORKS; DRUG-DELIVERY; G4; DENDRIMER; IN-VITRO; PAMAM G4; NANOPARTICLES; DOXORUBICIN; RELEASE;
D O I
10.1016/j.jddst.2022.103441
中图分类号
R9 [药学];
学科分类号
1007 ;
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 FTIR, 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.
引用
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页数:12
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