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.
Keywords: A549 lung cancer cell line; Cetuximab; Gene expression and regulation; MCF-7 breast cancer cell line; Polymeric nanoparticles; Stathmin-1.
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