Anti-Cancer Agents in Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 24(13), P. 1016 - 1028
Published: April 30, 2024
Although tamoxifen (TMX) belongs to selective estrogen receptor modulators (SERMs) and selectively binds receptors, it affects other estrogen-producing tissues due passive diffusion non-differentiation of normal cancerous cells leads side effects. The problems expressed about encouraged us design a new drug delivery system based on magnetic nanoparticles (MNPs) simultaneously target two receptors cancer through folic acid (FA) hyaluronic (HA) groups. mediator binding targeting agents MNPs is polymer linker, including dopamine, polyethylene glycol, terminal amine (DPN). Zeta potential, dynamic light scattering (DLS), Field emission scanning electron microscopy (FESEM) methods confirmed that MNPs-DPN-HA-FA has suitable size ~105 nm surface charge -41 mV, therefore, can be option for carrying TMX increasing its solubility. cytotoxic test showed the highest concentration MNPs-DPN-HA-FA-TMX decreased cell viability 11% after 72 h exposure compared control. While protective effect modified was evident, unlike tamoxifen, survival rate liver cells, even 180 min treatment, not significantly different from control group. also by examining amount malondialdehyde, no significant difference observed in lipid peroxidation caused Flow cytometry proved loaded onto induce apoptosis overexpressed cells. Real-time PCR activated intrinsic extrinsic mitochondrial pathways apoptosis, so Bak1/Bclx ratio MNPs-DPN-HAFA- free 70.82 0.38, respectively. Also, expression caspase-3 gene increased 430 times On hand, only TNF expression, which responsible metastasis some tumors, both MNPs-DPN-HA-FA-TMX. Finally, molecular docking could provide very stable interaction with CD44 folate reduce hepatotoxicity. All results show good affinity using metastatic breast ductal carcinoma T-47D lines. effects hepatocytes are quite they TMX.
Language: Английский