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

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.

Silver Nanoparticle-Coated Ethyl Cellulose Inhibits Tumor Necrosis Factor-α of Breast Cancer Cells.

INTRODUCTION: Cancer is one of the leading causes of death worldwide. In many cases, cancer is related to the elevated expression of a significant cytokine known as tumor necrosis factor-α (TNF-α). Breast cancer in particular is linked to increased proliferation of tumor cells, high incidence of malignancies, more metastases, and generally poor prognosis for the patient. The research sought to assess the effect of silver nanoparticles reduced with ethyl cellulose polymer (AgNPs-EC) on TNF-α expression in MCF-7 human breast cancer cells. METHODS: The AgNPs-EC were produced using the green synthesis reduction method, and their formation was proofed via UV-VIS spectroscopy. Furthermore, AgNPs-EC were characterized for their size, charge, morphology, Ag ion release, and stability. The MCF-7 cells were treated with AgNPs-EC. Then, the expression of TNF-α genes was determined through PCR in real time, and protein expression was studied using ELISA. RESULTS: The AgNPs-EC were spherical with an average size of 150±5.1 nm and a zeta-potential of -41.4±0.98 mV. AgNPs-EC had an inhibitory effect on cytokine mRNA and protein expression levels, which suggests that they could be used safely in the fight against cancer. AgNPs-EC cytotoxicity was also found to be non-toxic to MCF-7. CONCLUSION: Our data determined AgNPs-EC as a novel inhibitor of TNF-α production. These results are promising for developing novel therapeutic approaches for the future treatment of cancer with safe materials.