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Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone with anticancer properties, but its application is limited because of its low water solubility. To increase the bioavailability and water solubility of ART, we synthesized three series of poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) (PCL-PEG-PCL) tri-block copolymers. The structure of the copolymers was characterized by HNMR, FTIR, DSC and GPC techniques. ART was encapsulated inside micelles by a nanoprecipitation method which leading to the formation of ART/PCL-PEG-PCL micelles. The obtained micelles were characterized by DLS and AFM technique. The results showed that the average size of micelles was about 83.22 nm. ART was encapsulated into PCL-PEG-PCL micelles with encapsulation efficacy of 89.23 ± 1.41%. In vivo results demonstrated that this formulation significantly increased drug accumulation in tumours. Pharmacokinetic study in rats revealed that in vivo drug exposure of ART was significantly increased and prolonged by intravenously administering ART-loaded micelles when compared with the same dose of free ART. The MTT assay showed that bare PCL-PEG-PCL micelles is non-toxic to MCF7 and 4T1 cancer cell lines whereas the ART/PCL-PEG-PCL micelles showed a specific toxicity to both cancer cell lines. Therefore, the polymeric micellar formulation of ART based copolymer could provide a desirable process for ART delivery. [ABSTRACT FROM AUTHOR]

Zoledronic acid (ZA) is known as a potent bisphosphonate in osteogenic differentiation, but at high doses, it possesses toxic effects and causes decreased proliferation and differentiation of osteoblasts. Therefore, encapsulation of ZA into nanoparticles and control of its release is expected to promote differentiation of stem cells into osteoblasts. The present work aimed to develop a simple method for synthesis of monodisperse ZA-loaded chitosan (CS) nanoparticles. In this regard, we proposed a microfluidic synthesis of nanoparticles through the ionic cross-linking of CS in the presence of ZA without a crosslinker. The main advantages of these microfluidic generated nanoparticles were narrow size distribution and fine spherical shape. Conversely, the nanoparticles that were synthesized using a bulk mixing method had an irregular shape with a broad size distribution. Real-time PCR assay as well as alizarin red staining were used to evaluate the in-vitro osteogenic potential of the nanoparticles. The results indicated that the controlled release of ZA from the microfluidic system generated uniform nanoparticles, improving the osteogenic differentiation of mesenchymal stem cells. Additionally, this microfluidic device provided the well-controlled synthesis of novel nanoparticles with a modified CS macromolecular polymer for targeted drug delivery systems. [Display omitted] • The CS-ZA nanoparticles were prepared via ionic gelation of CS in the presence of ZA. • A microfluidic device was used for the well-controlled fabrication of nanoparticles. • MFCSZA0.5 showed higher ZA entrapment and sustained release of ZA compared to BCSZA. • The nanoparticles were able to deliver ZA to enhance the osteogenesis of MSCs. [ABSTRACT FROM AUTHOR]

Herein, iron-gold core shell magnetic nanoparticles Fe@Au NPs was investigated as contrasting agent in radiation therapy in the breast cancer. Assessment of cytotoxic and radio sensitizing potential was done by MTT method and Flow cytometry. Radiation was done using Co 60 source. The response of cells to treatment with radiation alone and radiation with nanoparticles was assessed. The study demonstrates that Fe@Au nanoparticles do not have considerable cytotoxic effects, but they increase the effectiveness of radiation that means the survival of the group without nanoparticles exposed to 5 Gy radiations is 75%while the group with nanoparticles is 33%. With 2 Gy radiations the survival of the two groups are 87% and 80% respectively. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 receptor (IGF-1R) is expressed in malignant and normal breast tissue, and its intermittent activation by multiple IGF-1 signaling pathways leads to neoplasm cell proliferation, impaired apoptosis, increased survival, and resistance to cytotoxic therapeutic agents. Therefore, simultaneous suppression of the receptor and its cognate ligand would be a powerful promising strategy inhibiting malignant phenotypes of breast cancer cells. In the present study, Methoxypoly(ethylene glycol) - Poly(caprolactone) was hybridized with Dimethyldioctadecylammonium bromide (DDAB) cationic lipid (mPEG-PCL-DDAB) nanoparticles (NPs) and used as a carrier for simultaneous delivery of lycopene and insulin-like growth factor 1 receptor-specific lycopene encapsulated-mPEG-PCL-DDAB nanoparticle/siRNA to MCF-7 breast cancer cells. Then, the antitumor effects of this construct were evaluated in vitro. The results demonstrated that the synthesized mPEG-PCL-DDAB nanoparticle had suitable physicochemical properties. The use of mPEG-PCL-DDAB nanoparticle-loaded anti-insulin-like growth factor 1 receptor-siRNA and lycopene dramatically induced the process of apoptosis and arrested cell cycle in the MCF-7 tumor cell lines. In general, the findings of this study demonstrated the potency of mPEG-PCL-DDAB nanoparticles for dual delivery of siRNA, and lycopene in breast cancer cell lines followed the induction of apoptosis. [ABSTRACT FROM AUTHOR]

Triblock poly(ε-caprolactone) - poly(ethylene glycol) - poly(ε-caprolactone) (PCL-PEG-PCL) copolymers were synthesized and used to prepare polymersomes for controlled release of lovastatin (LOV) as hydrophobic drug. Biodegradable PCL-PEG-PCL copolymer nanoparticles were prepared and the drug loading, release, release kinetics, and anti-cancer activity of these drugs was investigated. The PCL-PEG-PCL copolymer was synthesized by ring-opening polymerization of e-caprolactone in the presence of mPEG as the initiator and Sn(Oct)2 as the catalyst. The synthesized copolymers and nanoparticles were characterized by FTIR, 1H NMR, DLS, and AFM techniques. The efficiency of drug loading and release from nanoparticles in vitro was studied by UV-Vis spectrophotometry. Additionally, MTT assays on HFF-2 cell lines were performed for determining the biocompatibility of polymersomes. Finally, the antiproliferative activity of polymersomes was examined on MCF-7 breast cancer cell line. The obtained results showed that the average diameter of nanoparticles was less than 57 nm. The loading capacity and encapsulation efficiency of LOV was 16.1 ± 0.36% and 59.01 ± 0.78%, respectively. In vitro release study showed that the release rate of polymersomes depended on pH and was higher at lower pH than under neutral condition. The result of cell viability assay on the MCF-7 line proved that bare nanoparticles showed little inherent cytotoxicity whereas the LOV-loaded nanoparticles were cytotoxic. [ABSTRACT FROM AUTHOR]

In this study, iron oxide magnetic bovine serum albumin core–shell nanoparticles (BSA coated IONPs) with narrow particle size distribution were synthesized under one-pot reaction via the desolvation and chemical co-precipitation method. Functionalized IONPs were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques. Furthermore, vibrating sample magnetometer (VSM) analysis show these nanoparticles (NPs) have an excellent magnetic properties. Cellular toxicity of IONPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared core-shell NPs were performed. The presence of albumin as a biomolecule coating on the surface of IONPs showed an improving effect to reduce the cytotoxicity. The properties of the designed NPs propose the BSA coated IONPs as a promising candidate for multifunctional biomedical applications. [ABSTRACT FROM AUTHOR]

Stroke is the most common reason for adult disabilities and the second ground for death worldwide. Our previous study revealed that selegiline serves as an alternative candidate in transient hypoxia-ischemia. However, aggressive and restless behavior was observed in stroke-induced rats receiving 4 mg/kg selegiline. In comparison, 1 mg/kg selegiline could induce negligible therapeutic effects on mitochondrial dysfunction and histopathological changes. Therefore, we designed oral noisome-based selegiline attached to 4-(4-nitrobenzyl) pyridine to improve transient global ischemia by attenuating cognitive impairments, oxidative stress, and histopathological injury. The investigation was performed in transient hypoxia-ischemia-induced rats by oral administration of nanoformulation containing selegiline (0.25-1 mg/kg) for 4 weeks (3 times a week). Novel object recognition (NOR) was considered to evaluate their cognitive dysfunction. Oxidative stress parameters and brain histopathological assessments were determined following the scarification of rats. Outstandingly, our data demonstrated slower selegiline release from niosomes relative to free drug, which was also in a controlled manner. Our data confirmed significant improvement in cognitive behavior in the NOR test, an increase in glutathione level and total antioxidant power, a decline in MDA and protein carbonyl level, as well as a decreased number of dead cells in histopathological assessment after being exposed to (0.5-1 mg/kg) selegiline-NBP nanoformulation. These data manifested that the selegiline-NBP nanoformulation (0.5-1 mg/kg) could significantly reduce oxidative damage, cognitive dysfunction, and histopathological damage compared to transient hypoxia-ischemia rats, which is 20 times lower than the therapeutic dose in humans. Therefore, the proposed nanoformulation would be capable as an alternative candidate without side effects in stroke. [ABSTRACT FROM AUTHOR]

3‐Monochloropropane‐1,2‐diol (3‐MCPD) as a main source of food contamination has always been known as a carcinogenic agent. Kidney, liver, testis, and heart seem to be the main target organs for 3‐MCPD. Because oxidative stress and mitochondrial dysfunction have been realized to be involved in 3‐MCPD‐induced cytotoxicity, the present study aimed to investigate the probable toxicity mechanisms of 3‐MCPD in isolated mitochondria, HEK‐293 cell line, and cell isolated from the rats' liver and kidney through measuring multiparametric oxidative stress assay. Based on the data indicating no significant difference between 3‐MCPD‐treated groups and control group, metabolites of 3‐MCPD have a key role in organ toxicity caused by them. To further investigating the suggested hypothesis, the effect of 3‐MCPD toxicity on HEK‐293 cell line was examined. Although the proliferation declined after exposure to a low dose of 3‐MCPD (10 to 200 µM), controversial responses in higher concentration (2 to 10 mM) have led to studies on the effect of oxidative stress and cell death signaling on isolated kidney and liver cells. Treatment of the isolated kidney and liver cells with 3‐MCPD resulted in an increase in the level of reactive oxygen species (ROS), the collapse of mitochondrial membrane potential (MMP), and activation of cell death signaling without creating any significant difference in the amount of reduced glutathione. In fact, 3‐MCPD can disrupt the mitochondrial electron transfer in isolated cells, which is correlated with the impairment of mitochondrial oxidative phosphorylation system, the rise of ROS level, and the failure of MMP, leading to the release of cytochrome c from mitochondria to cytosol and finally the activation of cell death signaling. [ABSTRACT FROM AUTHOR]

Abstract Expansion of human induced pluripotent stem cells (h-iPSCs) on mouse derived feeder layers or murine cells secretions such as Matrigel hamper their clinical applications. Alternative methods have introduced novel substrates as stem cell niches or/and optimized combinations of humanized soluble factors as fully defined mediums. Accordingly vitronectin as a main part of ECM have been commercialized significantly as a stem cell niche-forming substrate. In this work, we used a functional peptide derived from vitronectin (VTN) and co-immobilized it with FGF-2 (as an indisputable ingredient of defined culture mediums) on chitosan film surface. After chemical and physical characterization of the pristine chitosan surface as well as ones modified by VTN or/and FGF-2, h-iPS cells were cultured on them at the xeno/feeder-free conditions. Our results demonstrated that co-immobilization of these two biomolecules has a synergistic effect on adhesion and clonal growth of h-iPS cells with maintained expression of pluripotency markers in a FGF-2 density-dependent manner. This is the first report of co-immobilization of an ECM derived molecule and a growth factor for stem cell culture. Graphical abstract Unlabelled Image Highlights • Co-immobilization of an ECM-derived peptide (i.e. vitronectin-derived peptide) and a growth factor (i.e. FGF-2) on the surface (i.e. chitosan film) was accomplished for the first time and confirmed by XPS, fluorometry and ELISA techniques. • The yield of each reaction revealing the surface density of each immobilized biomolecule was estimated which was neglected in the most of immobilization reports. • Feeder/xeno-free culture of human induced pluripotent stem cells (h-iPSCs) on chitosan based surfaces demonstrated that the co-immobilization of vitronectin and FGF-2 has a synergistic effect on attachment, proliferation and colony formation of h-iPS cells with the maintained expression of pluripotency markers in a FGF-2 density-dependent manner. [ABSTRACT FROM AUTHOR]

[Display omitted] • Co-delivery optimizes Alzheimer's treatment. • Surface modification with valine-conjugated chitosan for Alzheimer's therapy. • A brain-targeted nanocarrier exhibits superior memory restoration in AD models. Multifunctional nanocarriers are increasingly promising for disease treatment aimed at finding effective therapy and overcoming barriers in drug delivery. Herein, valine conjugated chitosan (VLCS) was used for surface modification of nanocarriers (NCs) based on Poly (ε-caprolactone)-Poly (ethylene glycol)-Poly (ε-caprolactone) (PCL-PEG-PCL) triblock copolymers (NCs@VLCS). The nanocarriers were co-loaded with rivastigmine (RV) and quercetin (QT) to yield the final RV/QT-NCs@VLCS as a multifunctional nanocarrier for Alzheimer's disease (AD) treatment. The large amino acid transporter 1 (LAT-1) was selected for the direction of the NCs to the brain. The biocompatibility of the nanocarrier was studied in HEK-293 and SH-SY5Y cells and rats. The Morris water maze test demonstrated a faster regain of memory loss with RV/QT-NCs@VLCS compared to the other groups. Furthermore, RV/QT-NCs@VLCS and RV/QT-NCs improved GSH depletion induced by scopolamine (SCO), with RV/QT-NCs@VLCS having a superior effect. The real-time PCR analysis revealed that co-delivery of RV and QT by NCs@VLCS showed significantly higher efficacy than sole delivery of RV. RV/QT-NCs@VLCS treatment also modulated the expression of BDNF, ACHE, and TNF-α. The findings revealed that NCs@VLCS co-loaded with RV and QT, significantly increased efficacy relative to the single use of RV and could be considered a potent multifunctional drug delivery system for Alzheimer's treatment. [ABSTRACT FROM AUTHOR]

Abstract: In this work we reported the synthesis of tamoxifen (TMX) loaded l-tyrosine natural amino acids (Tyr) modified Fe3O4 magnetic nanoparticles. Tyr, which was containing phenol groups was selected to study their effects on biocompatibility, loading capacity and release profile of TMX. TMX loaded Tyr modified Fe3O4 magnetic nanoparticles (F@Tyr@TMX NPs) were characterized by X-ray diffraction, thermo gravimetric analysis, Fourier transform infrared spectroscopy, vibrating sample magnetometer, dynamic light scattering and transmission electron microscopy techniques. The results showed that the ζ-potential of F@Tyr@TMX NPs was about − 12.8 mV and the average size was 22.19 ± 3.58 [mean ± SD (n = 50)] nm. The loading capacity of 11.34 ± 0.09% and encapsulation efficiency of 51.21 ± 0.41%. Additionally, hemolysis test and MTT assays on HEK-293 were performed for determination of biocompatibility of F@Tyr@TMX NPs. Finally, the anticancer activity of F@Tyr@TMX NPs studied on MCF-7 breast cancer cell lines. The results indicate that these as prepared magnetic nanoparticles are suitable for delivery of TMX and even other hydrophobic drugs.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Co-delivery approach has been recommended to reduce the amount of each drug and to achieve the synergistic effect for cancer treatment. Curcumin (CUR) and sulforaphane (SF) have antitumor effects, but their application is limited because of their low water solubility and poor oral bioavailability. To improve the bioavailability and solubility of SF and CUR, we performed an innovative co-delivery of them with PEGylated gold coated Fe3O4 magnetic nanoparticles (PEGylated Fe3O4@Au NPs) to endorse SF and CUR maintenance as an effective and promising antitumor drugs. The structure of the synthesized nanocarriers evaluated by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometer, dynamic light scattering and Fourier transform infrared spectroscopy. The results revealed that the zeta potential of CUR and SF-loaded NPs were about -15.4 mV and the average sizes were 80.57 nm. They were monodispersed (polydispersity index = 0.161 ± 0.016) in water with high drug-loading capacity and stability. CUR and SF were encapsulated into NPs with loading capacity of 17.32 ± 0.023% and 16.74 ± 0.015% and the entrapment efficiency of 83.72 ± 0.14% and 81.20 ± 0.18% respectively. The in-vitro study of SF and CUR loaded PEGylated Fe3O4@Au NPs on human breast adenocarcinoma cell line (MCF-7) confirmed that cytotoxicity of SF and CUR can enhance when they are loaded on PEGylated Fe3O4@Au NPs in comparison to free SF and CUR. The results of real-time PCR and flow cytometry shown that this combination can increase therapeutic effects of SF and CUR by apoptosis and necrosis induction as well as inhibiting of migration in MCF-7 cell line. [ABSTRACT FROM AUTHOR]

In this study, a kind of magnetic Fe3O4@mTiO2-GO (where m was shorted mesoporous) hybrids with core–shell nano-structure for controlled dual targeted drug delivery was synthesized using a facile sono-chemical method. The structure and chemical composition of the nanocarrier (NC), and its surface morphology, were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) with an energy dispersive X-ray (EDX), vibrating sample magnetometer (VSM) spectroscopy and Fourier transform infrared spectroscopy (FT-IR). Synthesis of Fe3O4@mTiO2-GO was proved by XRD and FT-IR. SEM showed that the particle size of this NC was in the range of ∼ 85–95 nm. EDX confirmed the presence of Ti, Fe, C and O in the nanocarrier. VSM analysis showed the magnetic behavior of the Fe3O4@mTiO2-GO nano-hybrids with saturation magnetization (MS) of 1.57 emu/g at room temperature. Curcumin (CUR) as a hydrophobic and an anti-tumor model drug was loaded on the NC. Drug loading capacity and encapsulation efficiency of this NC were as high as 17.85 and 72.45%, respectively. The drug release behavior was sustained and pH-responsive. MTT results demonstrated no significant cytotoxicity of the NC on Human Foreskin Fibroblast Normal cell line (HFF-2), indicating that this NC can be safe for use as a drug carrier for delivering anticancer drugs to tumor sites. The results of an MTT test on Caco-2 cancerous cells proved that CUR in nano-carriers has retained its anti-cancer properties. [ABSTRACT FROM AUTHOR]

We report the synthesis of iron oxide magnetic nanoparticles (IONPs) coated with various natural amino acids (AAs) using a one‐pot reaction in an aqueous medium. Several AAs, which contained hydrophilic and hydrophobic groups, were selected to study their effects on size, morphology and toxicity of IONPs. Functionalized IONPs were characterized using X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and scanning and transmission electron microscopies. Furthermore, vibrating sample magnetometry analysis shows these nanoparticles have excellent magnetic properties. Cellular toxicity of IONPs was also investigated on HFF2 cell lines. The AA‐coated IONPs are non‐toxic and biocompatible. Natural AA‐coated IONPs show a potential for their development in in vitro and in vivo biomedical fields due to their non‐toxicity, good ζ‐potential and related small size and narrow size distribution. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms of drug metabolisms by cytochrome P450 (P450s) could affect drug response, attracting particular interest in the pharmacogenetics. Due to the importance of CYP2C19* 17 allele and its capability of super- fast metabolism and also lack of information about distribution of the alleles in Iranian population, this research aimed to use High Resolution Melting (HRM) method compared to PCR-RFLP for genotyping healthy Iranian population. Methods: Blood samples were collected from 100 healthy Iranian volunteers. DNA was extracted by salting out method. Real-time PCR was used for amplification of the CYP2C19 gene and the alleles were identified by HRM. Sequencing was used to confirm the amplified DNA fragments and data were analyzed using SPSS software ver.18. Results: The frequency of alleles CYP2C19*1/*1, CYP2C19*1/*17 and CYP2C19*17/*17 were estimated as 58.33, 29.1 and 11.1%, respectively. Specificity and sensitivity of HRM method were 90% and 100%, with respect to PCR-RFLP. Also, HRM analysis has been evaluated as a faster and more effective approach. Conclusion: Comparison of our results based on HRM analysis with PCR-RFLP showed that our developed method is rapid, accurate, fast and economic to study the CYP2C19*17 allele and it is appropriate for other similar population genetic studies. [ABSTRACT FROM AUTHOR]

There was an incorrect labeling of the samples during the VSM experiment by the operator, which caused us to present an incorrect Ms for F@Tyr@TMX NPs in Fig. 6 revised below. Since the presented result is related to iron oxide nanoparticles, replacement of the image does not influence the main conclusions of the paper. In order to present valid results, we repeated the VSM experiments. [ABSTRACT FROM AUTHOR]

Correction for ‘Methotrexate-conjugated mPEG–PCL copolymers: a novel approach for dual triggered drug delivery’ by Kobra Rostamizadeh et al., New J. Chem., 2018, 42, 5937–5945. [ABSTRACT FROM AUTHOR]