Breast cancer suppression by curcumin-naringenin-magnetic-nano-particles: In vitro and in vivo studies

Abstract

BACKGROUND: The limitations of surgery, radiotherapy, and chemotherapy in cancer treatment and the increase in the application of nanomaterials in the field of biomedicine have promoted the use of nanomaterials in combination with radiotherapy for cancer treatment. OBJECTIVE: To improve the efficiency of cancer treatment, curcumin-naringenin loaded dextran-coated magnetic nanoparticles (CUR-NAR-D-MNPs) were used as chemotherapy and in combination with radiotherapy to verify their effectiveness in treating tumors. METHODS: CUR-NAR-D-MNPs were prepared and studied by several characterization methods. Median inhibitory concentration (IC50) and cellular toxicity were evaluated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell death and radiosensitization were studied by acridine orange/ethidium bromide dual staining of MCF-7 human breast cancer cells. RESULTS: CUR-NAR-D-MNPs induce apoptosis and inhibited cell proliferation through reactive oxygen species (ROS) generation. CUR-NAR-D-MNPs used alone had a certain therapeutic effect on tumors. CUR-NAR-D-MNPs plus radiotherapy significantly reduced the tumor volume and led to cell cycle arrest and induction of apoptosis through modulation of P53high, P21high, TNF-αlow, CD44low, and ROShigh signaling CONCLUSIONS: CUR-NAR-D-MNPs are effective in the treatment of tumors when combined with radiotherapy, and show radiosensitization effects against cancer proliferation in vitro and in vivo.

Naringenin and Hesperidin as Promising Alternatives for Prevention and Co-Adjuvant Therapy for Breast Cancer

“…However, cells incubated with CUR-NAR-D-MNPs 48 h before radiotherapy had exacerbated apoptosis and necrosis percentages compared to those that received radiotherapy, indicating this compound’s antiproliferative and radiosensitizing activity. When evaluating the effect of CUR-NAR-D-MNPs in female Sprague Dawley rats, the treatment reduced tumor volume, leading to cell cycle arrest and induction of apoptosis through modulation of signaling, high p53, high p21, low TNF-α, low CD44, and high RS [ 161 ].…”

Phytochemical-based nanodrugs going beyond the state-of-the-art in cancer management—Targeting cancer stem cells in the framework of predictive, preventive, personalized medicine

“…Moreover, curcumin combined with naringenin loaded dextran-coated magnetic nanoparticles (Cur-Nar-D-MNPs) inhibited cell proliferation and induced apoptosis through ROS production, increased P53 and P21, and decreased TNFα and CD44 in MCF-7 human breast cancer cells. Furthermore, CUR-NAR-D-MNPs reduced the tumor volume and caused the cell cycle arrest in DMBA-induced mammary tumor in rats ( Askar et al, 2021 ). Additionally, GANT61, a hexahydro pyrimidine derivative, can target CSCs of different types of human cancers through the GLI1 protein of the Hedgehog pathway.…”

Protective potential of naringenin and its nanoformulations in redox mechanisms of injury and disease

“…In addition, magnetic nanoparticles (MNPs) exhibit strong antioxidant activity and free radical-scavenging properties, due to electron transfer from the Fe +2 /Fe +3 systems of iron oxide nanoparticles [ 93 ]. In the work by Askar et al, in 2021 two natural polyphenols curcumin and NAR were loaded in dextran-coated magnetic nanoparticles (CUR-NAR-D-MNPs) and used as a radiosensitizer and chemotherapeutic agent to improve the effectiveness of curcumin-NAR in treating tumors [ 94 ]. Dextran is a water-soluble polysaccharide that can decrease the saturation magnetization of magnetic nanoparticles, thereby decreasing their cytotoxicity and increasing their biocompatibility [ 95 ].…”

“…This formulation is speculated to improve the cellular uptake and thereby higher accumulation of nanoparticles (NPs) inside the cancer cell. Further experiments revealed that oral administration of CUR-NAR-D-MNPs to breast cancer-bearing rats was associated with reduced tumor volume and cell cycle arrest possibly through modulation of P53high, P21high, TNF-low, CD44low, and ROS-high signaling [ 94 ].…”