Том 24, № 13 (2024)

Background:Limited chemotherapy efficacy and cancer stem cells (CSCs)-induced therapeutic resistance are major difficulties for tumour treatment. Adopting more efficient therapies to eliminate bulk-sensitive cancer cells and resistant CSCs is urgently needed.

Methods:Based on the potential and functional complementarity of gold and silver nanoparticles (AuNPs or AgNPs) on tumour treatment, bimetallic NPs (alloy) have been synthesized to obtain improved or even newly emerging bioactivity from a combination effect. This study reported a facile, green and economical preparation of Au-Ag alloy NPs using biocompatible polydopamine (PDA) as a reductant, capping, stabilizing and hydrophilic agent.

Results:These alloy NPs were quasi-spherical with rough surfaces and recorded in diameters of 80 nm. In addition, these alloy NPs showed good water dispersity, stability and photothermal effect. Compared with monometallic counterparts, these alloy NPs demonstrated a dramatically enhanced cytotoxic/pro-apoptotic/necrotic effect towards bulk-sensitive MCF-7 and MDA-MB-231 cells. The underlying mechanism regarding the apoptotic action was associated with a mitochondria-mediated pathway, as evidenced by Au3+/Ag+ mediated Mitochondria damage, ROS generation, DNA fragmentation and upregulation of certain apoptotic-related genes (Bax, P53 and Caspase 3). Attractively, these Au-Ag alloy NPs showed a remarkably improved inhibitory effect on the mammosphere formation capacity of MCF-7 CSCs.

Conclusion:All the positive results were attributed to incorporated properties from Au, Ag and PDA, the combination effect of chemotherapy and photothermal therapy and the nano-scaled structure of Au-Ag alloy NPs. In addition, the high biocompatibility of Au-Ag alloy NPs supported them as a good candidate in cancer therapy.

Background::Xanthenes and benzoxanthenesare are highly valuable compounds in organic chemistry and medicinal chemistry. Xanthene derivatives were found to have many applications in medicinal chemistry.

Objective::This work aims to explore the synthesis of xanthene derivatives with various substituents and find the possibility of their uses as anticancer agents.

Methods:The basic starting compound through this work was the 2,3-dihydro-1H-xanthen-1-one (3), which was synthesized from the reaction of cyclohexan-1,3-dione and 2-hydroxybenzaldehyde. Compound 3 was used to synthesize new thiophene, pyrimidine, isoxazole, and thiazole derivatives based on the xanthenes nucleus. Fused xanthene derivatives were obtained through further heterocyclization reactions. Multicomponent reactions expressed in this work were carried out in the presence of solvent catalyzed by Et3N and in solvent-free ionic liquid immobilized catalyst.

Results::Cytotoxicity for the newly synthesized compounds toward cancer cell lines was measured, and the results revealed that many compounds exhibited high inhibitions.

Conclusion::The antiproliferative activity of the synthesized compounds was studied on six selected cancer cell lines. The nature of the heterocyclic ring and the variations of substituted groups showed a high effect through the inhibitions of the tested compound.

Background:Although tamoxifen (TMX) belongs to selective estrogen receptor modulators (SERMs) and selectively binds to estrogen receptors, it affects other estrogen-producing tissues due to passive diffusion and non-differentiation of normal and cancerous cells and leads to side effects.

Methods:The problems expressed about tamoxifen (TMX) encouraged us to design a new drug delivery system based on magnetic nanoparticles (MNPs) to simultaneously target two receptors on cancer cells through folic acid (FA) and hyaluronic acid (HA) groups. The mediator of binding of two targeting agents to MNPs is a polymer linker, including dopamine, polyethylene glycol, and terminal amine (DPN).

Results:Zeta potential, dynamic light scattering (DLS), and Field emission scanning electron microscopy (FESEM) methods confirmed that MNPs-DPN-HA-FA has a suitable size of ~105 nm and a surface charge of -41 mV, and therefore, it can be a suitable option for carrying TMX and increasing its solubility. The cytotoxic test showed that the highest concentration of MNPs-DPN-HA-FA-TMX decreased cell viability to about 11% after 72 h of exposure compared to the control. While the protective effect of modified MNPs on normal cells was evident, unlike tamoxifen, the survival rate of liver cells, even after 180 min of treatment, was not significantly different from the control group. The protective effect of MNPs was also confirmed by examining the amount of malondialdehyde, and no significant difference was observed in the amount of lipid peroxidation caused by modified MNPs compared to the control. Flow cytometry proved that TMX loaded onto modified MNPs can induce apoptosis by targeting the overexpressed receptors on cancer cells. Real-time PCR showed that the modified MNPs activated the intrinsic and extrinsic mitochondrial pathways of apoptosis, so the Bak1/Bclx ratio for MNPs-DPN-HAFA- TMX and free TMX was 70.82 and 0.38, respectively. Also, the expression of the caspase-3 gene increased 430 times compared to the control. On the other hand, only TNF gene expression, which is responsible for metastasis in some tumors, was decreased by both free TMX and MNPs-DPN-HA-FA-TMX. Finally, molecular docking proved that MNPs-DPN-HA-FA-TMX could provide a very stable interaction with both CD44 and folate receptors, induce apoptosis in cancer cells, and reduce hepatotoxicity.

Conclusion:All the results showed that MNPs-DPN-HA-FA-TMX can show good affinity to cancer cells using targeting agents and induce apoptosis in metastatic breast ductal carcinoma T-47D cell lines. Also, the protective effects of MNPs on hepatocytes are quite evident, and they can reduce the side effects of TMX.