A dual catalytic functionalized hollow mesoporous silica-based nanocarrier coated with bacteria-derived exopolysaccharides for targeted delivery of irinotecan to colorectal cancer cells.

In this study, we introduced a multifunctional hollow mesoporous silica-based nanocarrier (HMSN) for the targeted delivery of irinotecan (IRT) to colorectal cancer cells. Due to their large reservoirs, hollow mesoporous silica nanoparticles are suitable platforms for loading significant amounts of drugs for sustained drug release. To respond to pH and redox, HMSNs were functionalized with cerium and iron oxides. Additionally, they were coated with bacterial-derived exopolysaccharide (EPS) as a biocompatible polymer. In vitro analyses revealed that cytotoxicity induced in cancer cells through oxidative stress, mediated by mature nanocarriers (EPS.IRT.Ce/Fe.HMSN), was surprisingly greater than that caused by free drugs. Cerium and iron ions, in synergy with the drug, were found to generate reactive oxygen species when targeting the acidic pH within lysosomes and the tumor microenvironment. This, in turn, triggered cascade reactions, leading to cell death. In vivo experiments revealed that the proposed nanocarriers had no noticeable effect on healthy tissues. These findings indicate the selective delivery of the drug to cancerous tissue and the induction of antioxidant effects due to the dual catalytic properties of cerium in normal cells. Accordingly, this hybrid drug delivery system provides a more effective treatment for colorectal cancer with the potential for cost-effective scaling up.

Tumor tropic delivery of FU.FA@NSs using mesenchymal stem cells for synergistic chemo-photodynamic therapy of colorectal cancer.

To overcome the limitations associated with the targeting abilities of nanotherapeutics and drug loading capacity of mesenchymal stem cells (MSCs), the present study relies on the combination of MSCs tumor tropism with the controlled release function of nano-based drug delivery platforms to achieve tumor-specific accumulation of chemotherapeutics with minimal off-target effects. 5-fluorouracil (5-FU)-containing ceria (CeNPs) coated calcium carbonate nanoparticles (CaNPs) were functionalized with folinic acid (FA) to develop drug-containing nanocomposites (Ca.FU.Ce.FA NCs). NCs were then conjugated with graphene oxide (GO) and decorated with silver nanoparticles (Ag°NPs) to form FU.FA@NS, a rationally designed drug delivery system with O2 generation capacity that alleviates tumor hypoxia for improved photodynamic therapy. Engineering of MSCs with FU.FA@NSs provided successful loading and long-term retention of therapeutics on the surface membrane with minimal changes to the functional properties of MSCs. Co-culturing of FU.FA@NS.MSCs with CT26 cells upon UVA exposure revealed enhanced apoptosis in tumor cells through ROS-mediated mitochondrial pathway. FU.FA@NSs released from MSCs were effectively taken up by CT26 cells via a clathrin-mediated endocytosis pathway and distributed their drug depots in a pH, H2O2, and UVA-stimulated fashion. Therefore, the cell-based biomimetic drug delivery platform formulated in the current study could be considered a promising strategy for targeted chemo-photodynamic therapy of colorectal cancer.

Mg.ATP-decorated ultrafine magnetic nanofibers: A bone scaffold with high osteogenic and antibacterial properties in the presence of an electromagnetic field.

In this study, ultrafine magnetic nanofibers were developed for bone regeneration purposes. Nanofibers were acquired by electrospinning using a two-component nanofiber matrix (CP: chitosan (Cs) and polyvinyl alcohol (PVA)) containing different concentrations of succinate conjugated-magnetic hydroxyapatite nanocomposites (SMHA). Hybrid nanofibers (CP&SMHA) containing 5 mg ml-1 of SMHA nanocomposite showed well-defined properties in terms of physicochemical properties and cell behavior. Then, they were modified with adenosine 5'-triphosphate (ATP) and Mg2+ ions. The initial adhesion of mesenchymal stem cells and their proliferation rate on the surface of modified nanofibers (Mg.ATP.CP&SMHA) were significantly increased as compared to those of bare nanofibers. Analysis of common osteogenic markers such as alkaline phosphatase activity and the expression of Runt-related transcription factor 2 and osteocalcin confirmed the osteogenic efficacy enhancement of CP&SMHA nanofibers when they were functionalized with ATP and Mg2+. The utilization of the antagonist of purine receptor, P2X7, revealed that this receptor has a major role in the osteogenesis process induced by Mg.ATP.CP&SMHA. Moreover, the results showed that cell adhesion, proliferation, and differentiation improved as nanofibers were under the influence of the electromagnetic field (EMF), displaying synergistic effects in the process of bone formation. Mg.ATP.CP&SMHA also showed an antibacterial effect against gram-negative and gram-positive bacteria, Escherichia coli and Staphylococcus aureus, respectively. Considering the high osteogenic potential and antibacterial activity of Mg.ATP.CP&SMHA nanofibers particularly in combination with EMF, it can serve as a great candidate for use in bone tissue engineering applications.

Tailoring the proliferation of fibroblast cells by multiresponsive and thermosensitive stem cells composite F127 hydrogel containing folic acid.MgO:ZnO/chitosan hybrid microparticles for skin regeneration.

In this study, biodegradable and thermosensitive F127 hydrogel containing folic acid.MgO:ZnO/chitosan hybrid particles (FMZC) was fabricated as a 3D mesenchymal stem cells (MSCs) delivery vehicle for regenerative medicine and wound healing purposes, in such a way to be responsive to lysozyme and UVA irradiation. The results showed that F127 hydrogel containing FMZC is a suitable and nontoxic construct for encapsulation of MSCs in the presence of lysozyme and UVA irradiation, bearing high stem cell viability and proliferation. The final hydrogel, MSC&FMZC, in response to lysozyme induced a higher proliferation rate and migration in human foreskin fibroblast cells (HFF). These phenomena were attributed to the released F.MgO:ZnO nanocomposites from chitosan microparticles and paracrine factors from MSCs within the hydrogel, resulting in synergistic biological effects. Moreover, lysozyme-treated MSC&FMZC hydrogel showed higher antibacterial and anti-biofilm activity against both Gram-positive and Gram-negative bacteria than bare hydrogel. However, a significant increase in the antibacterial activity of MSC&FMZC was observed as the treated bacteria were subjected to UVA irradiation owing to the photocatalytic activity of F.MgO:ZnO nanocomposites. Regarding the antibacterial activity and stimulating skin cell behavior of MSC&FMZC hydrogel that can promote the regenerative activities of skin, it could be considered as a promising scaffold for bacteria-accompanied wound healing.

Fenton-magnetic based therapy by dual-chemodrug-loaded magnetic hydroxyapatite against colon cancer.

Fenton-based therapy is emerging as an effective and selective strategy against cancer. However, a low concentration of transition metal ions, insufficient endogenous H2O2, and a high level of antioxidant activity within the cancer cells have hindered the therapeutic efficacy of this strategy. To address these issues, in this study, the Fenton reagent (magnetic hydroxyapatite, mHAP) was accompanied with chemotherapy drugs (cisplatin (CDDP) and methotrexate (MTX)) and static magnetic field (SMF), in such a way to be a pH-, redox-, and magnetic-responsive nanoplatform. In vitro and in vivo experiments revealed higher toxicity of the final construct, MTX.CDDP@mHAP, toward colon cancer cells, as compared with that of free drugs. The most effective antitumor activity was observed as MTX.CDDP@mHAP-treated tumor cells were exposed to SMF (0.9 T) and no noticeable damage was observed in the normal cells and tissues. Active targeting by MTX and magnetic targeting by mHAP under magnetic field increased the tumor selectivity and enhanced the tumor site accumulation and cellular uptake of MTX.CDDP@mHAPs. The released iron ions within the cancer cells trigger the Fenton reaction while the release of chemotherapy drugs, reduction of intracellular glutathione, and application of SMF aggravated the Fenton reaction, subsequently leading to the generation of reactive oxygen species (ROS) and induction of apoptosis. Therefore, Fenton magnetic-based therapy-mediated by MTX.CDDP@mHAP could be considered as a promising strategy against colon cancer with high therapeutic efficiency and biosafety.

Synthesis and characterization of lysozyme-conjugated Ag.ZnO@HA nanocomposite: A redox and pH-responsive antimicrobial agent with photocatalytic activity.

Hydroxyapatite (HA) is extensively used for implantable device coating; however, it lacks antibacterial property, leading to potential bacterial infection during orthopedic implantation surgery. Herein, to enhance the antibacterial activity of HA, a redox- and pH-responsive HA nanocomposite with photocatalytic activity was designed. A photosensitive heterostructure, zinc oxide/hydroxyapatite (ZnO.HA), was coated with Ag nanoparticles (AgNPs) with assisted gallic acid using the UV-irradiation method. An antibacterial enzyme, lysozyme, was then conjugated on the surface of the nanocomposite by a cleavable disulfide linker, resulting in a redox-sensitive nanoplatform. In comparison with bare HA, the designed nanocomposites as Lyso.CAGZ@HA displayed much higher antibacterial activity (> 5-fold) toward Escherichia coli (E. coli) owing to the synergistic antibacterial effects of ZnONPs, AgNPs, gallic acid, and lysozyme on the surface of the nanocomposite. However, antibacterial and antifouling effects are much more enhanced in Lyso.CAGZ@HA-treated bacteria as they were subjected to UVA irradiation. Moreover, the cellular uptake of nanocomposite and intracellular glutathione depletion enhanced in the presence of UVA light, resulting in reactive oxygen specious generation enhancement. Further, in vitro cytotoxicity experiments on mammalian cells (human foreskin fibroblast) revealed that nanocomposite has no cytotoxic effects. Hence, this study demonstrated that Lyso.CAGZ@HA could be considered as a potential therapeutic approach against bacterial infectious diseases.

Sono-synthesis approach improves anticancer activity of ZnO nanoparticles: reactive oxygen species depletion for killing human osteosarcoma cells.

Aim: To investigate the effect of ultrasound during the synthesis of ZnO nanoparticles (NPs) on their anticancer activity. Materials & methods: ZnO NPs were synthesized in the presence and absence of ultrasonic irradiation. Biological tests were performed on human osteosarcoma cancer cells (Saos-2). Results: The sono-synthesized sample indicated higher cytotoxicity than the conventional one. (IC50 = 16.48 ± 0.41 µg/ml for sonochemical ZnO; 26.96 ± 0.33 µg/ml for conventional ZnO). Both sonochemical and conventional samples acted like antioxidants and reduced intracellular reactive oxygen species level. This reduction was more significant in cells treated with the sono-synthesized sample. The sono-synthesized ZnO NPs showed more tumor selectivity than the conventional sample. Conclusion: Sono-synthesis of ZnO NPs by a bath sonicator could improve their anticancer activity.

A Correlation Between Intracellular Zinc Content and Osteosarcoma.

Zinc is a trace element in human body involved in many biological processes. It is critical for cell growth and acts as a cofactor for the structure and function of a wide range of cellular proteins such as enzymes. Mounting evidence has shown the involvement of intracellular zinc in the bone-related biological processes such as bone growth, homeostasis, and regeneration; however, the molecular mechanism(s) whereby zinc impels tumorigenesis in bone remains largely unexplored. In this article, selective outline related to the content of intracellular zinc in osteosarcoma cells was provided, and its correlation with signaling molecules that are activated and consequently guide the cells toward tumorigenesis or osteogenesis was discussed. Based on preclinical and clinical evidence, dysregulation of zinc homeostasis, both at intracellular and tissue level, has the main role in the pathogenesis of osteosarcoma. Based on the intracellular zinc content, this element could have a direct role in the dynamics of bone cell transformation and tumor development and play an indirect role in the modulation of the inflammatory and pro/antitumorigenic responses in immune cells. In this context, zinc transporters and the proteins containing zinc domain are regulated by the availability of zinc, playing a crucial role in bone cell transformation and differentiation. According to recent studies, it seems that intracellular zinc levels could be considered as an early prognosis marker. Besides, identification and targeting of zinc-dependent signaling molecules could tilt the balance of life and death toward the latter in chemoresistant malignant cells and may pave a way for designing of the novel osteosarcoma treatment strategies.

Enhanced osteogenesis properties of titanium implant materials by highly uniform mesoporous thin films of hydroxyapatite and titania intermediate layer.

Titanium (Ti) has been widely used for medical and dental applications; however, bare Ti cannot be properly connected to a living bone, and hence some modifications are needed for this purpose. The present study describes the synthesis of mesoporous hydroxyapatite thin films (MHF) on titanium implant materials for speeding up and shortening the processes of osteointegration. The uniform MHF was coated on a Ti substrate following the insertion of intermediate titania (TiO2) film via the sol-gel dip-coating method. The intermediate titania layer improved the bonding strength between the MHF and Ti substrate. MHFs were synthesized using a precursor solution containing phosphoric acid, calcium nitrate tetrahydrate, and a nonionic surfactant (C12E10) as the phosphate source, calcium source, and structure-directing agent, respectively. The effect of calcination temperature on phase composition, morphology, microstructure, roughness, and wettability of the MHFs was investigated using XRD, FE-SEM, COM, AFM, and contact angle measurement. The XRD results revealed the crystalline hydroxyapatite phase, which was improved with an increase in the calcination temperature. Moreover, the FE-SEM images showed the crack-free MHFs, uniform thickness of the layer, and mesoporous surface morphology. In addition, it was found that the roughness and wettability of the samples change upon the alteration of calcination temperature. The biological studies demonstrated that MHFs support the adhesion and proliferation of the mesenchymal stem cells (MSCs) and guid them toward osteogenic differentiation. Therefore, the MHFs prepared in this study may be useful in a wide range of applications, particularly in bone regeneration medicine.

Graphitic carbon nitride nanosheets prepared by electrophoretic size fractionation as an anticancer agent against human bone carcinoma.

Graphitic carbon nitride, g-C3N4, is a fascinating candidate for biomedical applications. Of course, bulk g-C3N4 is not appropriate for this purpose due to its large size distribution and low dispersion in water. Herein, for the first time, the electrophoretic size fractionation of g-C3N4 without introducing some functional groups into its structure was performed within a very short time. This simple separation technique resulted in several factions. The smallest collected fraction was nanosheets and showed the enhanced photoluminescence properties such as high PL intensity and bright luminescence. The nanosheets demonstrated significantly higher toxicity (IC50 of 27.0 ± 4.2 µg/ml- after 48 h) against human bone carcinoma cell line, Saos-2, in the absence of external light source compared to the bulk g-C3N4 (IC50 of 104.0 ± 8.5 µg/ml- after 48 h) without any cytotoxic effect on normal cells, human foreskin fibroblast.

In vitro cytotoxicity of polyphenols from Datura innoxia aqueous leaf-extract on human leukemia K562 cells: DNA and nuclear proteins as targets.

Leukemia is a malignant hematological disease and chemotherapy remains the most important tool for its treatment. As chemotherapy has many side effects and could lead to resistance in cancer cells, plant-based medication is being considered as a new strategy in cancer treatment. Datura innoxia from the Solanaceae family is used in traditional medicine. The present study investigated the effect of an aqueous extract of D. innoxia aqueous leaf-extract on human chronic myeloid leukemia cells (K562 cell line) and human B lymphoblastoid cells (FS-2 cells) as the noncancerous cell line. The interaction of the D. innoxia extract with double-stranded DNA and histones was studied using multiple spectroscopic techniques. The total phenolic and flavonoid contents were determined through colorimetric analysis and the major polyphenols were quantified by HPLC-DAD analysis. The results demonstrated that the D. innoxia extract inhibited proliferation of the K562 cell line in a dose- and time-dependent manner (IC50 = 0.6 mg/ml), but had a slightly toxic effect on human B lymphoblastoid cells. The spectroscopy results suggest that the D. innoxia extract interacted with both DNA and histones in solution and that D. innoxia could be suggested as an anticancer drug.

Meso-macroporous crack-free nanohydroxyapatite coatings templated by C12 E10 diblock copolymer on Ti6Al4V implant materials toward human osteoblast-like cells.

Meso-macroporous nanohydroxyapatite coatings (MHACs) were synthesized on Ti6Al4V implant materials calcined at different temperatures using a nonionic diblock copolymer template (C12 E10 ) by sol-gel and dip-coating methods. To improve the bonding strength between the substrate and coating, a TiO2 intermediate layer was applied on the surface of the substrates. The physicochemical and structural properties of MHAC samples were fully studied by X-ray diffraction, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, scanning probe microscopy, field-emission scanning electron microscopy (FESEM), Brunauer-Emmett-Teller method, and contact angle measurements. Based on the data obtained, the hydroxyapatite phase with a flower-like morphology was formed on the Ti6Al4V substrates in all of the samples. According to confocal optical microscopy and FESEM images, there was no macrocrack and microcrack on the MHACs, whereas they were accompanied by macroporosities and mesoporosities on top of the coatings. By increasing the calcination temperature from 500°C to 650°C, the crystallite sizes increased, while the surface roughness value and hydrophilicity decreased. A reduction in specific surface area and an increase in the pore diameters occurred as the calcination temperature increased. In addition, the assessment of protein adsorption behavior over the samples revealed that the adsorption amounts significantly increased as the substrates were coated with HAP; however, the affinity of surface for protein adsorption was strictly dependent on the surface topography and hydrophilicity. in vitro cellular assay disclosed a great cytocompatibility in terms of adhesion and proliferation in MHAC samples as compared with that in TiO2 -coated and bare substrates. Regarding the physicochemical properties and biological studies, MHAC calcined at 650°C was deemed optimal for bone tissue engineering.

Mesoporous superparamagnetic hydroxyapatite nanocomposite: A multifunctional platform for synergistic targeted chemo-magnetotherapy.

In the present study, the aim was to develop a magneto-responsive nanocomposite for application in drug delivery by the integration of magnetic nanoparticles into an inorganic architecture, hydroxyapatite. The magnetic mesoporous hydroxyapatite nanocomposites, MMHAPs, were synthesized using a template-free method and fully characterized by XRD, FT-IR, TEM, FE-SEM, VSM, ICP, BET, and UV-Vis spectroscopy. MMHAPs exhibited a rod-like shape with a structure of large mesopores and high surface area. A sample of the nanocomposites with well-defined properties, MMHAP(2), was selected as a carrier for delivery of chemotherapy drug, doxorubicin (Dox). Then, it was coated with polyethylene glycol (P) and folic acid (F), providing aqueous stability and tumor targeting, respectively. The evaluation of drug release profile revealed that the release of drug occurs in a time-staggered manner under low pH conditions, which simulate the internal condition of lysosome. More important, a significant drug release was observed under a static magnetic field (SMF), displaying a magnetically triggered release. According to the toxicity assessment, MMHAP(2) did not show any noticeable toxic effect against the tumor cells (Saos-2) and normal cells (HEK-293) up to 100 µg ml-1 in the presence or absence of SMF. In contrast, the drug-loaded nanocomposite, F.P.D@MMHAP(2), possesses high antitumor efficacy particularly in the presence of SMF. Moreover, it was found that the cellular internalization of F.P.D@MMHAP(2) could be increased by SMF, providing therapeutic efficiency enhancement. The high cytotoxic effect of F.P.D@MMHAP(2) with the help of SMF caused apoptosis in the tumor cells, which was preceded by a disturbance in the intracellular redox state and then caspase activation. Based on the data obtained, F.P.D@MMHAP(2) is a pH- and magneto-responsive platform opening up a new perspective in terms of its exploitation in cancer therapy.

Targeted delivery of adenosine 5'-triphosphate using chitosan-coated mesoporous hydroxyapatite: A theranostic pH-sensitive nanoplatform with enhanced anti-cancer effect.

In this Study, a pH-sensitive nanoplatform made up of chitosan (Cs) and mesoporous hydroxyapatite (HAP) was synthesized and employed for delivering of adenosine 5'-triphosphate (ATP). The fabricated system was decorated with folic acid (FA), providing both tumor targeting and imaging. The FA.Cs.ATP@HAP nanoparticles displayed enhanced colloidal stability and controlled drug release. In vitro biological experiments revealed that FA.Cs.ATP@HAP was internalized into the tumor cells with a high efficiency in a time-dependent manner and exhibited strong fluorescence within the cells. Compared with free ATP, the FA.Cs.ATP@HAP nanoparticles exhibited a significant inhibition effect against the proliferation of the tumor cells (Saos-2, T47D, and MCF7) in a dose-dependent manner, while no significant cytotoxic effect was observed in the normal cells (HEK-293), indicating the selective cytotoxicity of the fabricated nanosystem against the tumor cells. Also, the mechanism of action of FA.Cs.ATP@HAP was investigated, and it was found that it induces a high rate of apoptosis in the tumor cells through a decrease in mitochondrial membrane potential and caspase activation. Based on these findings, FA.Cs.ATP@HAP is a novel biomedical material with targeting, imaging, and high anticancer properties against tumor cells, and it could be considered as a promising candidate for cancer therapy.

Catechin-conjugated mesoporous hydroxyapatite nanoparticle: A novel nano-antioxidant with enhanced osteogenic property.

Hydroxyapatite is the main component of mineral phase of bone which is widely employed for coating metal implants and scaffold materials in synthetic bone grafts owing to its osteoinductive property. In order to improve the bioactivity of hydroxyapatite, mesoporous hydroxyapatite nanoparticles (MHAP) were synthesized and chemically functionalized with 3-aminopropyltriethoxysilane. The amine-functionalized nanoparticles were conjugated with a natural antioxidant, catechin (Cat), through a stable amide linkage. The true structure of the bioconstruct was confirmed by calculating condensed Fukui indices. The functionalized-hydroxyapatite nanoparticles (Cat@MHAP) showed an outstanding antioxidant activity, having reactivity toward hydroxyl and superoxide radicals larger than that of free catechin. To explore the bone cell responses to this material, multilayer nanoparticle films were prepared by MHAP and Cat@MHAP on a glass substrate. Afterward, the short- and long-term responses of cultured mesenchymal stem cells (MSCs), osteosarcoma cells (Saos-2), and doxorubicin-resistant cells (RSaos-2/Dox) on the surface of the prepared films were investigated. Both the MSCs and bone tumor cells selectively adhered onto Cat@MHAP surface as compared with glass and MHAP at initial culture time. Moreover, it was found that Cat@MHAP decreases the proliferation of Saos-2 and RSaos-2/Dox cells in a time-dependent manner, while it supports the growth of MSCs, indicating the ability of Cat@MHAP to distinguish tumor cells from normal ones. Further, Cat@MHAP promotes the osteogenic differentiation in both the MSCs and tumor cells, accompanied by the attenuation of intracellular ROS. From these results, Cat@MHAP is a novel "nano-antioxidant," which could be considered as a promising biomaterial in treating bone defects, particularly after surgery in osteosarcoma patients.

Multifunctional fluorescent titania nanoparticles: green preparation and applications as antibacterial and cancer theranostic agents.

Theranostic nanoparticles have attracted considerable attention in recently revolutionized medicine. Since the last decade, there has been a growing attempt to design various theranostic nanoparticles but difficulties still exist in the fabrication of their biocompatible one. Herein, fluorescent titania nanoparticles (FTN) were fabricated using a one-step green method. This FTN had ultra-high doxorubicin hydrochloride (DOX) loading capacity (encapsulation efficiency 95.50% and loading content 38.20%) that release the loaded drug in response to acidic pH. In vitro cytotoxicity experiments on human osteosarcoma (SaOs-2) and breast cancer (MCF-7) cell lines revealed superior anticancer efficacy (lowered the IC50 concentration by 3- and 5.5-fold for SaOs-2 and MCF-7 cells, respectively) and also better imaging for intracellular tracking of DOX/FTN relative to free DOX. Furthermore, the prepared nanoparticles showed efficient antibacterial activity against both gram-negative (Escherichia coli ATCC 25922) and gram-positive (Staphylococcus aureus ATCC 25923) bacteria. In this study, we have developed novel theranostic titania nanoparticles with inherent fluorescence property for cancer imaging and therapy.

Fabrication of poly(ethylene glycol)-coated mesoporous nanocomposite ZnO@Fe2O3 for methotrexate delivery: An integrated nanoplatform for dual-mode cancer therapy.

Although chemotherapy is an effective strategy for treatment of tumor cells, the non-specific distribution of chemotherapy drugs and their poor aqueous solubility result in impaired treatment and cause serious side effects in patients. In this study, mesoporous ZnO@Fe2O3 nanocomposite was fabricated and used as a platform for drug delivery. ZnO@Fe2O3 nanocomposite showed a high capacity for the adsorption of chemotherapy drug, methotrexate (MTX). Drug-loaded nanoparticle was coated with poly(ethylene glycol) (PEG), leading to the enhanced colloidal stability and good cytocompatibility. In order to improve tumor selective targeting of PEG-coated nanoparticles, it was also decorated with folic acid. Fabricated drug delivery system (F-P-M-ZnO@Fe2O3) was characterized by FT-IR, TGA, zeta potential, and UV-Visible spectroscopy. F-P-M-ZnO@Fe2O3 nanoparticles showed spatio-temporal drug release which was precisely controlled by pH and UVA light. In vitro biological studies on breast cancer cell lines (MCF-7 and T47D cells) revealed that F-P-M-ZnO@Fe2O3 nanoparticles can be internalized by clathrin-mediated endocytosis in energy-dependent and folate receptor-dependent manner. Cytotoxicity experiments showed that the treatment of tumor cells with both F-P-M-ZnO@Fe2O3 nanoparticle and UV irradiation causes better synergistic effect in inducing cellular apoptosis than the free drug and UV irradiation alone. Induction of apoptosis occurred following the mitochondrial membrane disruption and caspase activation. Moreover, F-P-M-ZnO@Fe2O3 did not affect normal cells, indicating the selective cytotoxic effect of fabricated nanosystem. From these data, F-P-M-ZnO@Fe2O3 is a dual-responsive nanoplatform which could be considered as an appropriate candidate for targeted chemo-phototherapy in cancer.

Methotrexate-F127 conjugated mesoporous zinc hydroxyapatite as an efficient drug delivery system for overcoming chemotherapy resistance in osteosarcoma cells.

The resistance of cancer cells to chemotherapeutic agents and the poor selectivity of drugs toward tumor cells are regarded as the main impediments in successful cancer therapy. Currently, the design and fabrication of stimulus-responsive drug delivery systems with high specificity toward cancer cells are gaining increasing attention and they show a promising potential for clinical applications. In this study, mesoporous zinc-substituted hydroxyapatite has been synthesized and served as a drug delivery vehicle owing to its biocompatibility and high drug loading capacity. The mesoporous nanoparticles were decorated with F127 and subsequently conjugated with methotrexate (MTX) through a stable amide linkage. Since folate receptors are overexpressed on many tumor cell surfaces, MTX on the nanocarrier system plays a dual role as a targeting molecule and a chemotherapeutic drug. The evaluation of the drug release profile revealed that MTX was cleaved from the nanoparticles by a certain type of enzyme under low pH conditions that are meant to simulate the intracellular conditions in the lysosome. Cell viability studies on primary osteosarcoma cells (Saos-2) and MTX-resistance cell lines (RSaos-2/MTX) revealed that the drug-loaded nanoparticles possess high antitumor efficacy on both of the cell lines relative to free MTX. It was also found that the inhibition of P-glycoproteins by F127 and the release of Zn2+ ions from the nanoparticles in an acidic environment effectively potentiate the antitumor efficacy of the drug-loaded nanoparticles, leading to caspase-mediated cell death. Based on these data, MTX-F127@ZnHAP nanoparticles are pH-responsive nanocarriers with precise controlled drug release and targeting effect. Therefore, they are considered to be promising candidates capable of overcoming resistance in osteosarcoma cells.

Antiplatelet Aggregation Activity of Walnut Hull Extract via Suppression of Reactive Oxygen Species Generation and Caspase Activation.

Walnut hull (wal hull) is an agricultural by-product that is widely used in traditional medicine for alleviating pain and treating skin diseases, however, recently it has gained much attention in modern pharmacology due to its antioxidant properties. The current study was aimed to determine the total phenolic, flavonoid, and tannin content of Persian wal hull extract and evaluate its biological effects on platelet function. Experimental data showed that acetone extract of wal hulls has a high content of polyphenolic compounds and antioxidant properties. The analytical study of crude extract by gas chromatography-mass spectrometry demonstrated different types of high- and low-molecular-weight compounds that are basically and biologically important. Moreover, an in vitro study revealed that wal hull extract at a concentration of 50 µg/mL inhibited thrombin-induced platelet aggregation and protein secretion by 50%, without any cytotoxic effects on platelets. The examined extract suppressed reactive oxygen species generation and also caspase activation in thrombin-stimulated platelets. Identically, N-acetylcysteine inhibited the increase of reactive oxygen species level induced by thrombin in platelets, and supported a link between cellular redox status and caspase activation in activated platelets. Presumably, the antiplatelet activity of wal hull extract is related to its polyphenolic compounds and their antioxidant properties. Therefore, wal hulls can be considered as a candidate for thrombotic disorders.

Acetone Extract of Almond Hulls Provides Protection against Oxidative Damage and Membrane Protein Degradation.

Several studies have revealed that among foods, the consumption of edible nuts has beneficial effects on health which are attributed to their high content of potent antioxidants. Among nuts, the whole seed of the almond (Prunus dulcis) has been demonstrated to possess potent free radical scavenging activity, which is related to the presence of phenolic compounds. The aim of the current study is to evaluate the polyphenol content and the antioxidant ability of almond hull, which is an agriculture solid waste. The present results revealed that among different extraction methods, the acetone extract of almond hulls has a high content of phenolic and flavonoid compounds and a high antioxidant ability, which were determined by using the phosphomolybdenum method and by measuring the potency of the antioxidant, respectively. Moreover, the experimental data disclosed that the acetone extract of almond hulls provides protection against the oxidative damage and the membrane protein degradation that are caused in human erythrocytes by hydrogen peroxide. These phenomena may likely be due to the recruitment of antioxidants by cell membranes and/or translocation to cytosol. Overall, almond hull extract could be considered as a natural source of antioxidants, and its consumption could have a positive effect on human health.