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

Abstract

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.

Magnetic hybrid nanomaterial based on a natural polymer and an amino acid as pH/temperature dual-responsive nanoplatform for the delivery of tamoxifen

“…The developed HMNP efficiently controlled the release of TMX under different release conditions (Figures 6A,B), acting as a promising nanocarrier for cancer nanomedicine. Consistent with the presented results, efficient control over TMX release has been previously reported for other HMNP based on Fe 3 O 4 nanoparticles coated with L-lysine and loaded with this drug (Rostami et al, 2021), thus confirming the potential use of Fe 3 O 4 -containing nanoplatforms for controlled delivery of anticancer therapeutics. As expected, TMX reference sample was released at a faster rate, independently of the medium and temperature.…”

“…Even some Fe 3 O 4 -AA conjugates have been used as nanocarriers in the treatment of cancer (Nosrati et al, 2018b;Nosrati et al, 2018c;Rostami et al, 2021), these functionalizations of MNP did not provide cancer-targeting properties. Therefore, to provide the final drug delivery nanoplatform targeting to cancer cells, HA was incorporated into the surface of Fe 3 O 4 -L-Cys nanoparticles (Figure 1).…”

“…There are several reports on the synthesis of AA-coated MNP using L-arginine, L-lysine, L-glutamine, glycine, L-tryptophan, L-tyrosine, and L-phenylalanine (Patron et al, 2008;Park et al, 2009;Viota et al, 2010;Jin et al, 2014;Nosrati et al, 2018a). Recently, methotrexate (Nosrati et al, 2018b) and tamoxifen (TMX) (Rostami et al, 2021) have been conjugated to L-lysine coated MNP for the inhibition of MCF-7 breast cancer cells. In addition, L-tyrosine-decorated MNP have been used as magnetic nanocarriers for TMX (Nosrati et al, 2018c).…”

Preparation and in Vitro Evaluation of Tamoxifen-Conjugated, Eco-Friendly, Agar-Based Hybrid Magnetic Nanoparticles for Their Potential Use in Breast Cancer Treatment

“…It was in agreement with a study reported by Rostami et al , where tamoxifen-loaded lysin-coated nanoparticles were found equally significant in controlling cell proliferation, as indicated by cell viability assays. In view of this, it is safe to suggest that TMX-AG-INPs are good candidates for breast cancer control evaluation after further studies …”

Magneto-Mechanically Triggered Thick Films for Drug Delivery Micropumps

“…Inorganic nanomaterials are modified so that they meet the requirements for their use in the systemic circulation to develop controlled and targeted therapies using a wide variety of small or large molecules [ 3 ]. Iron oxide nanoparticles, for instance, are widely explored in cancer treatment as drug delivery carriers [ 4 , 5 , 6 ] as well as in hyperthermia treatment [ 7 , 8 ]. Moreover, combining inorganic nanoparticles with stimuli-responsive materials led to a great improvement in cancer treatment by enhancing the drug cellular uptake and cytotoxicity of cancer cells.…”