The current study aimed to determine the protective effect of AY9944 related to Caveolin-1 and Claudin-5 role in lipid raft, which can rescue the blood-brain barrier from enhanced permeability. Therefore, in vivo analyses were performed following ischemia in normal, ischemic, and AY9944-treated animal groups. The results revealed that AY9944 reduced the infarct size, edema, and brain water content. The extravasation of Alb-Alexa 594 and biocytin-TMR was minimum in the AY9944-treated animals. The results showed a significant decrease in the expression level of Caveolin-1 over 8 h and 48 h and a remarkable increase in the level of Claudin-5 over 48 h following ischemia in AY9944-treated animals. Molecular docking simulation demonstrated that AY9944 exerts a possible protective role via attenuating the interaction of the Caveolin-1 and cholesterol in lipid raft. These findings point out that AY9944 plays a protective role in stroke by means of blood-brain barrier preservation. Proper neural function essentially needs a constant homeostatic brain environment which is provided by the blood-brain barrier. Rescuing blood-brain barrier from enhanced permeability via inducing the protective effect of AY9944 related to caveolin-1 and claudin-5 role in lipid raft was the aim of the current study.
In this study, a magnetic core-shell modified tumor-targeting nanocarrier (MNPs-PEG-TRA) was engineered and demonstrated for the efficient in vitro and in vivo hyperthermia treatment of breast cancer. Magnetic nanoparticles were used as the initial nanocarriers and modified via PEGylation followed by immobilization of Trastuzumab (TRA) with tumor-targeting function towards cancer cells. The hyperthermia performance of the developed targeting drug delivery system was explored using an in vitro study with SK-BR-3 cancer cells and an in vivo study using animal models (mouse) with DMBA-induced breast cancer. The average size of the engineered system was about 100 nm and its zeta potential was about +13 mV, whereby the stability of the system in biological media is enormously enhanced while the possibility of it being removed via the immune system is diminished. The investigation was pursued based on comparing the changes in growth inhibition rates of HSF 1184, MDA-MB-231, MDA-MB-468 and SK-BR-3 cell lines at different temperatures (37 °C, 40 °C, 42 °C, and 45 °C). Compared with bare MNPs and MNPs-PEG, a remarkably enhanced hyperthermia effect using MNPs-PEG-TRA was observed not only in cultured SK-BR-3 cells in vitro but also in an in vivo DMBA tumor bearing mice model. These results are attributed to an about 4 fold higher concentration of MNPs-PEG-TRA carriers in the tumor site compared to the other organs confirming the considerable potential of the magnetic tumor-targeting hyperthermia concept for breast cancer treatment.
Engineering of a physiologically compatible, stable and targetable SPIONs-CA-FA formulation was reported. Initially fabricated superparamagnetic iron oxide nanoparticles (SPIONs) were coated with citric acid (CA) to hamper agglomeration as well as to ameliorate biocompatibility. Folic acid (FA) as a targeting agent was then conjugated to the citric acid coated SPIONs (SPIONs-CA) for targeting the specific receptors expressed on the FAR+ cancer cells. Physiochemical characterizations were then performed to assure required properties like stability, size, phase purity, surface morphology, chemical integrity and magnetic properties. In vitro evaluations (MTT assay) were performed on HeLa, HSF 1184, MDA-MB-468 and MDA-MB-231cell lines to ensure the biocompatibility of SPIONs-CA-FA. There were no morphological changes and lysis in contact with erythrocytes recorded for SPIONs-CA-FA and SPIONs-CA. High level of SPIONs-CA-FA binding to FAR+ cell lines was assured via qualitative and quantitative in vitro binding studies. Hence, SPIONs-CA-FA was introduced as a promising tool for biomedical applications like magnetic hyperthermia and drug delivery. The in vitro findings presented in this study need to be compared with those of in vivo studies.
Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.