High efficacy of tamoxifen-loaded L-lysine coated magnetic iron oxide nanoparticles in cell cycle arrest and anti-cancer activity for breast cancer therapy

• Published in: Bioimpacts Vol. 12; no. 4; pp. 301 - 313
• Main Authors: Rostami, Soheila, Tafvizi, Farzaneh, Kheiri Manjili, Hamid Reza
• Format: Journal Article
• Language: English
• Published: Tabriz Tabriz University of Medical Sciences 01-07-2022; Tabriz University of Medical Sciences (TUOMS Publishing Group)
• Subjects: Amino acids; Antitumor activity; Antitumor agents; Apoptosis; Breast cancer; Cancer therapies; Cell cycle; Cell growth; Chemotherapy; Cytotoxicity; Differential scanning calorimetry; Drug delivery; Drug delivery systems; Drug development; Drug resistance; Efficiency; Endocytosis; Iron oxides; l-lysine; Light scattering; Localization; Lysine; magnetic iron oxide nanoparticles; mcf-7 cell line; Morphology; Nanoparticles; Nanotechnology; Original Research; Pharmacokinetics; Scanning electron microscopy; Side effects; Size distribution; Spectrum analysis; Tamoxifen; Toxicity; Transmission electron microscopy; Vagina; X-ray diffraction; United Kingdom > UK; Iran; Germany
• ISSN: 2228-5660; 2228-5652; 2228-5660
• DOI: 10.34172/bi.2021.23337

Introduction: Due to the side effects of drugs, the development of nanoscale drug delivery systems has led to a significant improvement in medicinal therapies due to drug pharmacokinetics changes, decreased toxicity, and increased half-life of the drug. This study aimed to synthesize tamoxifen (TMX)-loaded L-lysine coated magnetic iron oxide nanoparticles as a nano-carrier to investigate its cytotoxic effects and anti-cancer properties against MCF-7 cancer cells. Methods: Magnetic Fe3O4 nanoparticles were synthesized and coated with L-lysine (F-Lys NPs). Then, TMX was loaded onto these NPs. The characteristics of synthesized nanoparticles (F-Lys-TMX NPs) were evaluated by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). The drug release was analyzed at pH 5.8 and pH 7.4. The MCF-7 cells were exposed to F-Lys-TMX NPs, F-Lys NPs, and TMX for 24, 48, and 72 hours. To evaluate the cytotoxic potential of designed nanoparticles, MTT and apoptosis assays, real-time PCR, and cell cycle analysis was carried out. Results: The F-Lys-TMX NPs had spherical morphology with a size ranging from 9 to 30 nm. By increasing the nanoparticles concentration and treatment time, more cell proliferation inhibition and apoptosis induction were observed in F-Lys-TMX NPs-treated cells compared to the TMX. The expression levels of ERBB2, cyclin D1, and cyclin E genes were down-regulated and expression levels of the caspase-3 and caspase-9 genes were up-regulated. Studies on the drug release revealed a slow and controlled pH-dependent release of the nanoparticles. Cell cycle analysis indicated that F-Lys-TMX NPs could arrest the cells at the G0/G1 phase. Conclusion: The findings suggest that F-Lys-TMX NPs are more effective and have the potential for cell proliferation inhibition and apoptosis induction compared to the TMX. Hence, F-Lys-TMX NPs can be considered as an anti-cancer agent against MCF-7 breast cancer cells.