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PEG-4000 formed polymeric nanoparticles loaded with cetuximab downregulate p21 & stathmin-1 gene expression in cancer cell lines.

Abdellatif, AAH, Tolba, NS, Alsharidah, M, Al Rugaie, O, Bouazzaoui, A, Saleem, IY, Maswadeh, H and Ali, AT (2022) PEG-4000 formed polymeric nanoparticles loaded with cetuximab downregulate p21 & stathmin-1 gene expression in cancer cell lines. Life Sciences, 295. ISSN 0024-3205

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Abstract

Cetuximab (CTX) is known to have cytotoxic effects on several human cancer cells in vitro; however, as CTX is poorly water soluble, there is a need for improved formulations can reach cancer cells at high concentrations with low side effects. We developed (PEG-4000) polymeric nanoparticles (PEGNPs) loaded with CTX and evaluated their in vitro cytotoxicity and anticancer properties against human lung (A549) and breast (MCF-7) cancer cells. CTX-PEGNPs were formulated using the solvent evaporation technique, and their morphological properties were evaluated. Further, the effects of CTX-PEGNPs on cell viability using the MTT assay and perform gene expression analysis, DNA fragmentation measurements, and the comet assay. CTX-PEGNP showed uniformly dispersed NPs of nano-size range (253.7 ± 0.3 nm), and low polydispersity index (0.16) indicating the stability and uniformity of NPs. Further, the zeta potential of the preparations was -17.0 ± 1.8 mv. DSC and FTIR confirmed the entrapping of CTX in NPs. The results showed IC50 values of 2.26 μg/mL and 1.83 μg/mL for free CTX and CTX-PEGNPs on the A549 cancer cell line, respectively. Moreover, CTX-PEGNPs had a lower IC50 of 1.12 μg/mL in MCF-7 cells than that of free CTX (2.28 μg/mL). The expression levels of p21 and stathmin-1 were significantly decreased in both cell lines treated with CTX-PEGNPs compared to CTX alone. The CTX-PEGNP-treated cells also showed increased DNA fragmentation rates in both cancer cell lines compared with CTX alone. The results indicated that CTX-PEGNP was an improved formulation than CTX alone to induce apoptosis and DNA damage and inhibit cell proliferation through the downregulation of P21 and stathmin-1 expression.

Item Type: Article
Uncontrolled Keywords: 0601 Biochemistry and Cell Biology, 1115 Pharmacology and Pharmaceutical Sciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
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Date Deposited: 06 Apr 2022 11:23
Last Modified: 06 Apr 2022 11:30
DOI or Identification number: 10.1016/j.lfs.2022.120403
URI: https://researchonline.ljmu.ac.uk/id/eprint/16609

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