ABSTRACT
Objective: To explore the effect and mechanism of dihydroartemisinin (DHA) in inducing ferroptosis of tumor cells. Methods: 3,3',5,5'-Tetramethylbenzidine was used to detect the oxygen free radicals (•OH) formed by DHA and FeSO4 in vitro. The cytotoxicity of DHA on HepG2 cells was detected by MTT method (including FeSO4 or deferoxamine pretreated groups). MTT assay was used to investigate the influence of glutathione (GSH) and inhibitor (Fer-1) on cytotoxicity of DHA; DCFH-DA dye was used to investigate intracellular reactive oxygen species induced by DHA (including FeSO4 pretreated groups). C11-BODIPY581/591 and DiO dye were used to examine the influence of DHA (including FeSO4 pretreated groups) on intracellular lipid peroxide formation and cell membrane structure; Glutathione peroxidase assay kit was used to explore the influence of DHA (including FeSO4 pretreated groups) on intracellular activity GPX-4 in HepG2 cells. Results: Fenton-like reaction occurred between DHA and Fe2+, and •OH was produced during the reaction. The half-inhibitory concentration (IC50) of DHA was (39.96 ± 8.78) μmol/L. FeSO4 and deferoxamine could increase or decrease the cytotoxicity of DHA, respectively. After treated with DHA, the intracellular content of reactive oxygen species and lipid peroxide was increased, the cell morphology became larger, and the cell membrane was broken. Compared with the DHA treated group, the FeSO4 pretreated group further increased the intracellular reactive oxygen species and lipid peroxide content, and the cell membrane morphology was completely destroyed. FeSO4 could also enhance the inhibitory effect of DHA on GPX-4 activity. Conclusion: DHA increases intracellular reactive oxygen species through Fenton-like reaction and ultimately induces ferroptosis of tumor cells. In addition, exogenous iron can accelerate the Fenton-like reaction of DHA and accelerate the occurrence and development of ferroptosis of tumor cells.
ABSTRACT
Mesoporous silica nanoparticles (MSNs) have been widely used as drug carriers in the diagnosis and treatment of diseases due to their specific characteristics, which include a large surface area, ordered mesoporous structures, easy surface modification and feasible sustained release action for encapsulated drugs. With the research development of MSNs, the biodegradability and removability of mesoporous silica nanomaterials have attracted considerable attention in the clinical application of the MSNs-based formulations. This paper was prepared to emphasize the preparation approaches of biodegradable mesoporous silica nanoparticles through the metal oxide doping method and the organic compound doping method. We discussed the biodegradable mechanism and process of such nanoparticles, and finally, provided an insightful and helpful review of the prospective application of the biodegradable mesoporous silica nanoparticles in medical field.
ABSTRACT
A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.