PEG-4000 formed polymeric nanoparticles loaded with cetuximab downregulate p21 &amp; stathmin-1 gene expression in cancer cell lines
Authors: Nahla Sameh Tolba
Hamzah Maswadeh
Imran Saleem
Asmaa T Ali
Mansour Alsharidah
Ahmed A H Abdellatif
Osamah Al Rugaie
Abdellatif Bouazzaoui
Journal: Life Sciences (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: A549 lung cancer cell line; Cetuximab; Gene expression and regulation; MCF-7 breast cancer cell line; Polymeric nanoparticles
Affiliations: Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt. Electronic address: ., Department of Pharmaceutics, Faculty of Pharmacy, Sadat City University, Monufia 32897, Egypt. Electronic address: ., Department of Physiology, College of Medicine, Qassim University, Buraydah 51452, Saudi Arabia. Electronic address: ., Department of Basic Medical Sciences, College of Medicine and Medical Sciences, Qassim University, Unaizah, P.O. Box 991, Al Qassim 51911, Saudi Arabia. Electronic address: ., Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia; Science and Technology Unit, Umm Al-Qura University, Makkah 21955, Saudi Arabia.; Medical Clinic, Hematology/Oncology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg 93053, Germany. Electronic address: ., School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Liverpool L3 3AF, UK. Electronic address: ., Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia., Department of Biochemistry, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 Unexpected repetitions: ![file] , 
 [Corrigendum](http: www.sciencedirect.com science article pii S0024320522002818) published in the July issue of the journal. The explanation given by the authors sounds compelling: several images were overlapped by mistake in the original figure. It s nice to see a genuine mistake corrected in that way. , 
 The corrected TEM iamge is here (compare with #1): ![file] ,