Search

Doxorubicin is one of the most effective chemotherapeutic agents; however, it has various side effects, such as cardiotoxicity. Therefore, novel methods are needed to reduce its adverse effects. Quercetin is a natural flavonoid with many biological activities. Liposomes are lipid-based carriers widely used in medicine for drug delivery. In this study, liposomal doxorubicin with favorable characteristics was designed and synthesized by the thin-film method, and its physicochemical properties were investigated by different laboratory techniques. Then, the impact of the carrier, empty liposomes, free doxorubicin, liposomal doxorubicin, and quercetin were analyzed in animal models. To evaluate the interventions, measurements of cardiac enzymes, oxidative stress and antioxidant markers, and protein expression were performed, as well as histopathological studies. Additionally, cytotoxicity assay and cellular uptake were carried out on H9c2 cells. The mean size of the designed liposomes was 98.8 nm, and the encapsulation efficiency (EE%) was about 85%. The designed liposomes were anionic and pH-sensitive and had a controlled release pattern with excellent stability. Co-administration of liposomal doxorubicin with free quercetin to rats led to decreased weight loss, creatine kinase (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), while it increased the activity of glutathione peroxidase, catalase, and superoxide dismutase enzymes in their left ventricles. Additionally, it changed the expression of NOX1, Rac1, Rac1-GTP, SIRT3, and Bcl-2 proteins, and caused tissue injury and cell cytotoxicity. Our data showed that interventions can increase antioxidant capacity, reduce oxidative stress and apoptosis in heart tissue, and lead to fewer complications. Overall, the use of liposomal doxorubicin alone or the co-administration of free doxorubicin with free quercetin showed promising results. [ABSTRACT FROM AUTHOR]

Using a chemotherapeutic agent, such as doxorubicin (DOX), with a natural agent, such as silibinin (Sili), is highly valuable to minimize systemic toxicity. However, Sili and DOX face disadvantages, such as low aqueous solubility and poor bioavailability. Here, we have engineered a drug delivery cargo by decorating carboxylated graphene oxide (cGO) with an aptamer, HB5, for simultaneous delivery of DOX and Sili as a combination therapy against MCF-7 and SK-BR-3 breast cancer cells. The resulting Apt-cGO displayed a typical sheet-like nanostructure with a broad surface. The maximum entrapment efficiency was 70.42% and 84.22% for Sili and DOX, respectively. When the Apt-cGO-DOX-Sili nanocomposites were selectively taken up by breast cancer cells, the interaction between cGO and drugs was cleaved, causing releasing both Sili and DOX into the tumor cells, respectively. Compared to free drugs, Apt-cGO-DOX-Sili nanocomposites displayed higher cytotoxicity in vitro. Apt-cGO-DOX-Sili nanocomposites potentially suppressed some cancer cell survival signals. They accelerated cell apoptosis and increased Rb levels as well as reduced Akt, mTOR, NF-κB, and CDK2 levels. In conclusion, the developed Apt-cGO-DOX-Sili can be suggested as a simple and efficient drug delivery approach for breast chemotherapy. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are important tumor markers that indicate early metastasis, tumor recurrence, and treatment efficacy. To identify and separate these cells from the blood, new nanomaterials need to be developed. The present study explored the potential application of ZnFe2O4 magnetic nanoparticles in capturing CTCs with cell surface markers. Folic acid was coupled to l-cysteine-capped ZnFe2O4 nanoparticles (ZC) to provide binding sites on ZnFe2O4 nanoparticles for the recognition of folate bioreceptors, which are highly expressed in MCF-7 breast cancer cells. The cytotoxicity of ZnFe2O4 nanoparticles and ZC against MCF-7 was analyzed with the MTT assay. After 24 h of incubation, there were IC50 values of 702.6 and 805.5 µg/mL for ZnFe2O4 and ZC, respectively. However, after 48 h of incubation, IC50 values of ZnFe2O4 and ZC were reduced to 267.3 and 389.7 µg/mL, respectively. The cell quantification was conducted with magnetically collected cells placed on a glassy carbon electrode, and the differential pulse voltammetry (DPV) responses were analyzed. This cost-effective ZnFe2O4-based biosensing platform allowed cancer cell detection with a limit of detection of 3 cells/mL, ranging from 25 to 104 cells/mL. In future, these functionalized zinc ferrites may be used in electrochemical cell detection and targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Objective(s): One of the effective strategies for targeted chemotherapy of cancer is the use of lipid nanocarriers. In this study, an optimal formulation of niosomal drug containing doxorubicin was developed to monitor the potency against cancer cells. Materials and Methods: In this experimental study, niosomal vesicles were prepared using phosphatidylcholine (20%), span60 (52.5%), cholesterol (22.5%), and DSPE-PEG2000 (5%) by the thin-film method. Doxorubicin was loaded into the niosomes using an inactive loading method. Results: The features and characteristics of the nanocarrier were evaluated using Zeta-Sizer, SEM, FTIR, drug release, cellular uptake, and the cytotoxicity of the nanodrug carrier system by the MTT method. Niosomal vesicles-containing doxorubicin showed a size of ~156.8 nm, drug encapsulation efficiency of ~94.18%, zeta potential of ~-3.52 mV, and polydispersity index (PDI) of ~0.265. The prepared niosomes indicated a drugcontrolled release system and FTIR analysis showed no interaction between nanocarriers containing drug and doxorubicin. Moreover, morphological examination of nanocarriers using SEM microscopy revealed that they had spherical structures. Also, cellular studies showed that drug toxicity was higher in encapsulated form of the drug compared with non-encapsulated doxorubicin which was confirmed by the cellular uptake results. Conclusion: The results confirmed the proper physicochemical characteristics of these nanocarriers that significantly increased the toxicity of the encapsulated drug against the KG-1 cell line. It seems niosomal nanocarriers can be considered suitable carriers for drug delivery to cancer cells. [ABSTRACT FROM AUTHOR]

Objective(s): Due to the inefficiency of current treatment methods in the treatment of various cancers, as well as increasing antibiotic resistance in bacteria and fungi, attention to the use of medicinal plants and their essential oils is increasing. However, leading barriers to the use of plant essential oils, such as rapid oxidation and high volatility, highlight the need for a drug delivery system to increase their efficiency. Materials and Methods: Therefore, this study aimed to investigate the antimicrobial, antifungal, and cytotoxic effects of free thyme essential oil (TEO) and compare it with its nanoniosomal form. Initially, the chemical component of TEO was analyzed by the gas chromatography method. Then, to improve biopharmaceutical properties and enhance the stability of TEO in light and volatility, nanoniosomes containing thyme essential oil synthesized by thin-film hydration method and their physicochemical properties such as size and zeta potential, morphology, encapsulation efficiency (EE%), and profile of in vitro release were investigated. Results: The results showed that the nanoparticles had an average size of 97 nm with a zeta potential of -37 mV. Also, in the optimal formula, the EE% of essential oil in nanoniosomes and the maximum release rate of the TEO from nanosystem were 81% and 57%, respectively. On the other hand, it was found that the antibacterial and antifungal activity of TEO remarkably increased after encapsulation. Also, the cytotoxicity assay of TEO on cancer cells showed that blank nanoniosome had no cytotoxicity and besides, the IC50 of TEO in encapsulated form decreased by 1.75 times on MCF-7 cancer cells compared with its free form, which indicates an increase in its anti-cancer properties. Conclusion: Overall, encapsulation of thyme essential oil in optimal synthesized nano systems improved its anticancer and antimicrobial properties, which could be the beginning of a revolution in the treatment of cancer and microbial diseases using nano-encapsulated herbal remedies. [ABSTRACT FROM AUTHOR]

Objective: In obesity, chronic low grade inflammation, created by induction of pro-inflammatory markers, causes adipocyte dysfunction in adipose tissue. Adipocytes dysfunction is associated with various diseases including insulin resistance and obesity. In obesity, inflammatory factors such as osteopontin (OPN), angiopoietin-like protein 2 (Angptl2) and transforming growth factor-β (TGF-β) are induced in adipose tissue. Metformin and pioglitazone that are used to modulate inflammation, but the relevant mechanism is poorly understood. This study aimed to investigate the effect of metformin and pioglitazone as anti-diabetic drugs, on gene expression of osteopontin, Angptl2 and TGF-β as inflammatory factors in insulin resistance and hypertrophied adipocyte in 3T3-L1 cell line model in vitro. Materials and Methods: In this experimental research, we differentiated3T3-L1 preadipocytes to adipocytes. The adipocytes treated in insulin resistance and hypertrophied conditions with metformin and pioglitazone and assayed gene expression of OPN, Angptl2 and TGF-β by Real-Time PCR. Data was analyzed by SPSS statistic software. Results: The results showed that expression of OPN, Angptl2, and TGF-β were increased significantly over 2-fold (P-value< 0.05) in insulin resistance and hypertrophied adipocytes compared to normal adipocytes. Pre- and co-treatment with metformin and pioglitazone led to reduced expression of Angptl2 and TGF-β. Only metformin significantly reduced the expression of Angptl2, TGF-β and OPN in hypertrophied adipocyte. Conclusion: These results support the proposal that metformin and pioglitazone reduce gene expression of inflammatory factors in insulin resistant and hypertrophied adipocytes. [ABSTRACT FROM AUTHOR]

The aim of this study was to optimize the cationic PEGylated niosome-containing anti-cancer drugs and siRNA to enhance the therapeutic response. Therefore, various surfactant-based (tween-60) vesicles of doxorubicin (DOX; a chemotherapeutic drug) and quercetin (QC; a chemosensitizer) were prepared. To load siRNA on niosomes, 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) was used as a cationic lipid. The optimum formulation containing tween-60:cholesterol:DPPC:DOTAP:DSPE-PEG2000 at 49.5:5.5:15:25:5 demonstrated that the vesicle size and zeta potential were 52.8 ± 2.7 nm and +27.4 ± 2.3 mV, respectively. Entrapment efficiency (EE%) for DOX and QC was 86.4 ± 2.1% and 94.9 ± 3.9%, respectively. Moreover, the drug release during 6 h was 32.1 ± 1.6% and 30.5 ± 1.3% for DOX and QC, respectively denoted on the controlled release. The gel retardation assay demonstrated that siRNA could be successfully loaded into a cationic niosome:siRNA in a weight ratio 40:1. Additionally, noisome-encapsulated drugs had a higher toxicity against cancer cells when compared with un-encapsulated forms and the synergistic effects of co-delivery of siRNA and DOX with QC on gastric, prostate, breast cancer cells as well as human foreskin fibroblast as a normal cell line was shown. The results showed that the co-delivery of drugs and siRNA using cationic PEGylated niosomes exhibited an increased anti-cancer activity against the tumor cell death. It seems that cationic PEGylated niosomes have opened up a new avenue to enrich the armamentarium of therapeutic agents to fight cancer. [ABSTRACT FROM AUTHOR]

Background: 1, 25-dihydroxy Vitamin D3 (VitD) attenuates left ventricular hypertrophy (LVH), but the mechanisms remain to be portrayed in-depth. The small GTPase Rac1 plays a pivotal role in cardiovascular pathology, especially LVH. Here, we tested whether VitD exerts its anti-LVH effects by counteracting the small GTPase Rac1 expression., Methods: In Wistar rats, pressure overload-induced LVH was created by abdominal aortic banding. The animals were intraperitoneally administered VitD (0.1 µg/kg/d). Blood pressure was measured via carotid artery cannulation. Real-time RT-PCR and Western blotting were performed to assess the mRNA and protein expression, respectively. Myocardium was stained for determination of cardiomyocytes area and fibrosis. Lipid peroxidation levels and the activities of antioxidant enzymes were measured in left ventricular tissue., Results: VitD significantly reduced hypertrophy markers (blood pressure, heart-to-body weight ratio, cardiomyocytes area, fibrosis as well as atrial and brain natriuretic peptides mRNA levels) compared to untreated groups (P < 0.05). VitD also improved the activity of antioxidant enzymes and reduced lipid peroxidation levels in the myocardium (P < 0.05). LVH hearts of untreated animals displayed a significant increase in Rac1 expression compared with the control group (P < 0.05). In contrast, cardiac Rac1, at either mRNAs or protein levels, was markedly lower in LVH animals receiving VitD compared with their untreated counterparts (P < 0.05)., Conclusion: Our findings attest that VitD mitigates hallmarks of LVH imparted by pressure overload. Notably, VitD appears to perform its anti-LVH function partly through small GTPase Rac1 suppression. This, in turn, provides a robust incentive to consider VitD before LVH culminates in HF devastating disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)