Acellular spinal cord scaffold containing quercetin-encapsulated nanoparticles plays an anti-inflammatory role in functional recovery from spinal cord injury in rats.

Inflammatory responses play a crucial role in the pathophysiology of spinal cord injury (SCI) and developing new approaches to establish an anti-inflammatory environment for the promotion of neuroregeneration holds promise as a potential approach. In this study, our aim was to investigate the potential of combining an acellular spinal cord scaffold (ASCS) with quercetin-loaded bovine serum albumin (Qu/BSA) nanoparticles (NPs) for the treatment of SCI. The ASCS was prepared using physical and chemical methods, while the Qu/BSA NPs were prepared through a desolvation technique. The NPs exhibited favorable characteristics, including a mean size of 203 nm, a zeta potential of -38, and an encapsulation efficiency of 96%. Microscopic evaluation confirmed the successful distribution of NPs on the walls of ASCS. Animal studies revealed that Qu/BSA NPs group exhibited a significant decrease in NLRP3, ASC, and Casp1 gene expression compared to the SCI group (p < 0.0001). The findings indicated a significant decrease in the NLRP3, ASC, and Casp1 protein level between the Qu/BSA/ASCS group and the SCI group (p < 0.0001). Moreover, treatment with ASCS containing either blank BSA (B/BSA) NPs or Qu/BSA NPs effectively promoted functional recovery via increasing the amount of nestin- and glial fibrillary acidic protein (GFAP)-positive cells in the site of injury. Notably, Qu/BSA/ASCS exhibited superior outcomes compared to B/BSA/ASCS. Overall, the combination of ASCS with the Qu delivery system presents a promising therapeutic approach for SCI by inhibiting inflammatory responses and promoting neuroregeneration, leading to the restoration of motor function in animals. This study demonstrates the potential of utilizing biomaterials and NPs to enhance the effectiveness of SCI treatment.

Neurological recovery and neurogenesis by curcumin sustained-release system cross-linked with an acellular spinal cord scaffold in rat spinal cord injury: Targeting NLRP3 inflammasome pathway.

In the context of treating spinal cord injury (SCI), the modulation of inflammatory responses, and the creation of a suitable region for tissue regeneration may present a promising approach. This study aimed to evaluate the effects of curcumin (Cur)-loaded bovine serum albumin nanoparticles (Cur-BSA NPs) cross-linked with an acellular spinal cord scaffold (ASCS) on the functional recovery in a rat model of SCI. We developed an ASCS using chemical and physical methods. Cur-BSA, and blank (B-BSA) NPs were fabricated and cross-linked with ASCS via EDC-NHS, resulting in the production of Cur-ASCS and B-ASCS. We assessed the properties of scaffolds and NPs as well as their cross-links. Finally, using a male rat hemisection model of SCI, we investigated the consequences of the resulting scaffolds. The inflammatory markers, neuroregeneration, and functional recovery were evaluated. Our results showed that Cur was efficiently entrapped at the rate of 42% ± 1.3 in the NPs. Compared to B-ASCS, Cur-ASCS showed greater effectiveness in the promotion of motor recovery. The implantation of both scaffolds could increase the migration of neural stem cells (Nestin- and GFAP-positive cells) following SCI with the superiority of Cur-ASCS. Cur-ASCS was successful to regulate the gene expression and protein levels of NLRP3, ASC, and Casp1in the spinal cord lesion. Our results indicate that using ASCS can lead to the entrance of cells into the scaffold and promote neurogenesis. However, Cur-ASCS had greater effects in terms of inflammation relief and enhanced neurogenesis.

Combination nanochemotherapy of brain tumor using polymeric nanoparticles loaded with doxorubicin and paclitaxel: An in vitro and in vivo study.

This study aims to overcome physiological barriers and increase the therapeutic index for the treatment of glioblastoma (GBM) tumors by using Paclitaxel (PTX) loaded Poly(lactic co-glycolic acid) nanoparticles (PTX-PLGA-NPs) and Doxorubicin (DOX) loaded Poly (lactic co-glycolic acid) nanoparticles (DOX-PLGA-NPs). The hydrodynamic diameter of nanoparticles (NPs) was characterized by dynamic light scattering (DLS) which was 94 ± 4 nm and 133 ± 6 nm for DOX-PLGA-NPs, and PTX-PLGA-NPs, respectively. The zeta potential for DOX-PLGA-NPs and PTX-PLGA-NPs were -15.2 ± 0.18 mV and -17.3 ± 0.34 mV, respectively. The cytotoxicity of PTX-PLGA-NPs and DOX-PLGA-NPs was augmented compared to DOX and PTX on C6 GBM cells. The Lactate dehydrogenase (LDH) tests for various formulations were carried out. The results indicated that the amount of released LDH was 262 ± 7.84 U.L-1 at the concentration of 2 mg/mL in the combination therapy, which was much higher than other groups (DOX-PLGA-NPs (210 ± 6.92 U.L-1), PTX-PLGA-NPs (201 ± 8.65 U.L-1), DOX (110 ± 9.81 U.L-1), PTX (95 ± 5.02 U.L-1) and PTX + DOX (67 ± 4.89 U.L-1)). MRI results of the combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs indicated that GBM tumor size decreased considerably compared to the other formulations. Also, combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs demonstrated a longer median survival of more than 80 days compared to PTX (38 days), DOX (37 days) and PTX + DOX (48 days), PTX-NPs (58 days) and DOX-NPs (62 days). The results of locomotion, body weight, rearing and grooming assays indicated that combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs had the most positive effect on the movements of rats compared to the other formulations.

Electrochemical immunosensor based on carbon nanofibers and gold nanoparticles for detecting anti-Toxoplasma gondii IgG antibodies.

An electrochemical immunosensor based on carbon nanofibers (CNFs) and gold nanoparticles (AuNPs) was developed for detecting anti-Toxoplasma gondii antibodies  (anti-T. gondii) IgG in human serum. CNFs were produced using electrospinning and carbonization processes. Screen-printed carbon electrode (SPCE) surface was modified with CNFs and AuNPs which were electrodeposited onto the CNFs. Then, T. gondii antigen was immobilized onto the AuNPs/CNFs/SPCE. Afterward, anti-T. gondii IgG positive serum samples were coated on the modified electrode and assessed via adding anti-human IgG labeled with horseradish peroxidase (HRP) enzyme. The morphology of SPCE, CNFs, and AuNPs/CNFs/SPCE surface was characterized using field emission scanning electron microscopy (FESEM) equipped with energy dispersive spectroscopy (EDS). Characterization of CNFs was evaluated by Raman spectroscopy and X-ray diffraction (XRD). Electrochemical characterization of the immunosensor was verified using cyclic voltammetry (CV), and electrochemical response of modified electrode for anti-T. gondii IgG was detected via differential pulse voltammetry (DPV). This immunosensor was detected in the range 0-200 U mL-1 with a low detection limit (9 × 10-3 U mL-1). In addition, the proposed immunosensor was exhibited with high selectivity, strong stability, and acceptable reproducibility and repeatability. Furthermore, there was a strong correlation between results obtained via the designed immunosensor and enzyme-linked immunosorbent assay (ELISA) as gold standard. In conclusion, the developed immunosensor is a promising route for rapid and accurate clinical diagnosis of toxoplasmosis.

Effect of folate-targeted Erlotinib loaded human serum albumin nanoparticles on tumor size and survival rate in a rat model of glioblastoma.

The aim of this study was to prepare folate-targeted Erlotinib loaded human serum albumin nanoparticles (FA-ERL-HSA NPs) and investigate in vitro cytotoxic and apoptotic effects using cell lines (U87MG and C6 cells) and an in vivo rat bearing C6 glioma model. The mean size of the FA-ERL-HSA NPs prepared using a desolvation method was 135 nm. In vitro MTT assays demonstrated that FA-ERL-HSA NPs had an IC50 value of 52.18 µg/mL and 17.53 µg/mL compared to free ERL which had an IC50 value of 119.8 µg/mL and 103.2 µg/mL for U87MG and C6 cells for 72 h, respectively. Flow cytometry results showed the apoptosis rate with FA-ERL-HSA NPs (100 µg/mL, 72 h) was higher compared to free ERL for both U87MG and C6 cells. Experiments using a rat glioblastoma model via TUNEL assay indicated that the apoptosis index of FA-ERL-HSA NPs was 48 % compared to 21 % for free ERL and the tumor size effectively decreased after a daily injection of 220 µg (2.5 mg/kg) from 87.45 mm3 (19th day) to 1.28 mm3 (60th day). The median survival rate of the rats increased after treatment to >100 days which was greater than controls.

Antibacterial Activity and Toxicity of Zinc Oxide Nanoparticles Combined with Supernatants of Lactobacillus spp. Against ESKAPE Bacteria: A Novel Mixture.

Background: The emergence of multidrug resistance among nosocomial pathogens has prompted researchers to look for new antibacterial sources. Metal nanoparticles and probiotic products have attracted the attention of researchers. However, combination therapy is an attractive alternative in this field. Objectives: This study evaluated the antibacterial activity and toxicity of Zinc Oxide nanoparticles (ZnO-NPs) combined with cell-free supernatant (CFS) of Lactobacillus plantarum and Lactobacillus acidophilus alone and in a novel mixture. Methods: Antibacterial effects and cytotoxic properties of ZnO-NPs, CFS of L. plantarum (SLP), and CFS of L. acidophilus (SLA) were determined alone and in a mixture against ESKAPE strains. In addition, the viability percentage of the cells was evaluated after exposure to these agents. Results: Antibacterial mixtures (ZnO-NPs with SLP or ZnO-NPs with SLA) demonstrated synergistic and additive effects against Pseudomonas aeruginosa (FIC≤0.75), Acinetobacter baumannii (FIC = 1), and Escherichia coli (FIC≤0.75). The viability percentage of the cells after 24 h of exposure to a mixture of ZnO-NPs and SLA (about 50%) was more than when the cells were exposed to ZnO-NPs alone (about 30%) at the same concentration. Conclusions: A mixture of ZnO-NPs and CFS of probiotics can be an alternative to antibiotics, with more effectiveness and fewer side effects.

Polymeric nanoparticles for drug delivery in glioblastoma: State of the art and future perspectives.

Glioblastoma (GBM) is an aggressive, fatal and malignant primary brain tumor. Despite the current standard treatment for glioblastoma patients including neurosurgical resection, followed by concomitant radiation and chemotherapy, the median survival rate is only about 15 months. An unresolved challenge for current therapies is related to getting drugs through the blood-brain barrier (BBB), which hinders many chemotherapeutic agents from reaching tumors cells. Although a large amount of research has been done to circumvent the BBB and deliver drugs to the brain, with nanoparticles (NPs) taking the lead, the challenge is still high. In this regard, the BBB and how to transfer drug pathways through the BBB, especially using NPs, are introduced here. Afterwards, the latest advances in drug delivery, co-drug delivery, and combination modalities are described specifically for GBM treatments using natural and synthetic polymeric NPs and adjuvant therapies including hyperthermia, photodynamic therapy and also ketogenic regimens. In addition, receptor-mediated endocytosis agents that exist in endothelial capillary cells of the brain are explained. Lastly, future directions to finally deliver drugs through the BBB for GBM treatment are emphasized. It is the hope that this review can provide a number of practical pathways for the future development of BBB permeable nanochemotherapeutics against GBM.

Recent advances in gold nanoparticle-based colorimetric aptasensors for chemical and biological analyses.

Aptasensors are amazing among many currently formed procedures due to their excellent particularity, selectivity and responsiveness. These biosensors get more popular in combination with gold nanoparticles (AuNPs) to detect chemical and biological molecules. The response of AuNPs by changing color provides a simple explanation of outcomes. The authors review the recent developments in AuNP-based colorimetric aptasensors designed to sense different chemical and biological molecules. They summarize the procedure of AuNP-based detection and the ordinary instances of currently formed AuNP-based colorimetric procedures. Furthermore, their uses for detecting different analytes based on analyte types are given and the present challenges, overview, and positive views for forming new aptasensors are also regarded.

Yogurt fortified with omega-3 using nanoemulsion containing flaxseed oil: Investigation of physicochemical properties.

Flaxseed oil as a natural ingredient has many health benefits due to the rich contents of omega-3 fatty acids. However, its use in food formulations is limited because of low aqueous solubility, easy oxidation owing to the unsaturated nature of the fatty acids such as omega-3. The aim of this study was to prepare a stable nanoemulsion containing flaxseed oil and investigate the fortification of yogurt with this nanoemulsion compared with fortification with bulk flaxseed oil. The nanoemulsion of flaxseed oil-in-water was obtained by low-energy emulsification method. Optimized nanoemulsion contains 3% (w/w) flaxseed vegetable oil, 36% (w/w) surfactant, 10% (w/w) co-surfactant, and 51% (w/w) deionized water as a continuous phase. The result of transmission electron microscopy (TEM) showed that the optimal size was about 60 nm, which was stayed stable for 11 months. The results of gas chromatography (GC) indicated that the amount of omega-3 in nanoemulsion containing flaxseed oil was 27.3% and 19.8% after 7 days and 11 months, respectively. The turbidity results indicated the transparency of nanoemulsion after 11 months as well. The results of centrifuge experiments and thermal stress cycles exhibited that the optimized nanoemulsion was physically stable without any sign of creaming, phase separation, and cracking. In addition, pH and acidity of the yogurt fortified with nanoemulsion containing flaxseed oil were 4.22 and 1.41 wt%, respectively. In conclusion, fortifying yogurt with the nanoemulsion containing flaxseed oil can be considered as a solution to increase solubility, bioavailability, and protection of omega-3.

Designing a fluorescence padlock probe-based biosensor and colorimetric assay for the detection of G12D KRAS mutation.

Aim: Cell-free DNA in the plasma is known to be a potential biomarker for noninvasive diagnosis of oncogenic mutations. The authors aimed to design an optimized padlock probe-based hyperbranched rolling circle amplification biosensor to detect the KRAS G12D mutation using fluorescence and colorimetric methods. Methods: Single-factor experiments, Plackett-Burman design and response surface methodology were applied to optimize the padlock probe-based hyperbranched rolling circle amplification reaction. Results: The maximum fluorescence intensity was achieved at a padlock probe concentration of 1.5 pM and target concentration of 9 pM at 38°C ligation temperature. The proposed biosensor has a low detection limit of 60 fM of target DNA and a linear response in the concentration range of 60 fM to 0.2 pM. Conclusion: The results indicated the power of these assays to detect KRAS point mutations in liquid state reactions.

Effect of Paclitaxel/etoposide co-loaded polymeric nanoparticles on tumor size and survival rate in a rat model of glioblastoma.

The aim of this work is to co-load paclitaxel (PTX) and etoposide (ETP) in methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (mPEG-PLGA NPs) to overcome pharmacokinetics and physiological limitations and enhance therapeutic efficacy for treating intracranial glioblastoma. Both drugs were loaded into mPEG-PLGA NPs by a nano-precipitation method. The resultant NPs demonstrated an enhanced cytotoxic effect indicated by lower IC50 values and augmented cell apoptosis to U87 and C6 glioma cell lines compared to both free drugs. Additionally, blood compatibility assays showed that the PTX/ETP co-loaded mPEG-PLGA NPs did not induce blood hemolysis, blood clotting, or platelet aggregation. In vivo anti-glioma efficacy evaluation in rats bearingintracranialC6glioma revealed a superior anti-glioma activity for the treatment with PTX/ETP co-loaded mPEG-PLGA NPs compared to other formulations, particularly a significantly longer median survival, 76 days compared to 36 days for free PTX and 37 days for free ETP treatment, respectively, and higher tumor regression, proved by magnetic resonance imaging (MRI).

Paclitaxel/methotrexate co-loaded PLGA nanoparticles in glioblastoma treatment: Formulation development and in vitro antitumor activity evaluation.

AIM: The aim of this study was to improve the therapeutic index of chemotherapeutic drugs on glioblastoma cells through an improved co-drug delivery system. MATERIALS AND METHODS: Methotrexate (MTX) and paclitaxel (PTX) were co-loaded into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with polyvinyl alcohol (PVA) and Poloxamer188 (P188). KEY FINDINGS: The mean size of the NPs was about 212 nm, with a zeta potential of about -15.7 mV. Encapsulation efficiency (EE%) and drug loading (DL%) were determined to be 72% and 4% for MTX and 85% and 4.9% for PTX, respectively. The prepared NPs were characterized by differential thermal analysis (DTA) and thermogravimetric analysis (TGA). Moreover, an in vitro sustained release profile was observed for both drug loaded PLGA NPs. Glioblastoma cellular uptake of the NPs was confirmed by fluorescence microscopy and cell survival rate was investigated through the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method after 48 h of incubation showing IC50 values of 24.5 µg·mL-1 for PTX and 9.5 µg·mL-1 for MTX for the MTX/PTX co-loaded PLGA nanoparticles coated with PVA/P188 (Co-2 NPs). Apoptosis and necrosis were also studied via flow cytometry, the lactate dehydrogenase (LDH) assay and the amount of anti-apoptotic protein (Bcl-2) expression. Blood compatibility of the co-delivery of PTX and MTX loaded PLGA NPs was investigated using a hemolysis method as well. SIGNIFICANCE: The co-delivery of PTX and MTX loaded PLGA NPs is promising for the treatment of glioblastoma compared to their respective free drug formulations and, thus, should be further investigated.

Development of a Novel Electroactive Cardiac Patch Based on Carbon Nanofibers and Gelatin Encouraging Vascularization.

Tissue engineering makes it possible to fabricate scaffolds that can help the function of defective tissues or even the most complex organs such as the heart. Carbon nanofibers (CNFs), because of their high mechanical strength and electrical properties, can improve the functional coupling of cardiomyocytes and their electrophysiological properties. In this study, electroactive CNF/gelatin (Gel) nanofibrous cardiac patches were prepared by an electrospinning method. Scanning electron microscope (SEM) evaluation of prepared scaffolds showed randomly oriented nanofibers. The electrical conductivity of the CNF/Gel scaffolds was assessed by a four-probe device and was in the semiconducting range (~ 10-5 S/m). The result of an MTT assay confirmed the excellent biocompatibility of electroactive CNF/Gel scaffolds. Also, CNF-containing scaffolds supported cardiomyocyte adhesion and increased expression of the cardiac genes including TrpT-2, Actn4, and Conx43 compared with the non-conductive counterpart. Our findings also confirmed the angiogenic potential of CNF/Gel scaffolds as compatible and electroactive platforms for cardiac tissue engineering.

Investigation of Effective Parameters on Size of Paclitaxel Loaded PLGA Nanoparticles.

Purpose: The size of polymeric nanoparticles is considered as an effective factor in cancer therapy due to enterance into tumor tissue via the EPR effect. The purpose of this work was to investigate the effective parameters on poly(lactic-co-glycolic acid)-paclitaxel (PLGA -PTX) nanoparticles size. Methods: We prepared PLGA-PTX nanoparticles via single emulsion and precipitation methods with variable paremeters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration. Results: PLGA-PTX nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The results exhibited that the diameter of nanoparticles enhanced with increasing drug, polymer and PVA concentrations whereas organic to aqueous phase volume ratio and sonication time required to the optimization for a given size. Conclusion: The precipitation method provides smaller nanoparticles compared to emulsion one. Variable parameters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration affect diameter of nanoparticles.

Biocompatibility and nanostructured materials: applications in nanomedicine.

There has been huge interest in applications of nanomaterials in biomedical science, including diagnosis, drug delivery, and development of human organs. Number of these nanomaterials has been already studied in human or at pre-clinical trial. There is a growing concern on potential toxicity and adverse effects of nanomaterials on human health, including lack of standard method of assessment of toxicology of these materials. Our investigation indicated that the bare and small nanoparticle have higher toxicity than modified and bulk materials, respectively. In addition, spherical nanoparticles have less toxicity than rod nanoparticles due to immune response of body.

Nano-structures mediated co-delivery of therapeutic agents for glioblastoma treatment: A review.

Glioblastoma is a malignant brain tumor and leads to death in most patients. Chemotherapy is a common method for brain cancer in clinics. However, the recent advancements in the chemotherapy of brain tumors have not been efficient enough. With the advancement of nanotechnology, the used drugs can enhance chemotherapy efficiency and increase the access to brain cancers. Combination of therapeutic agents has been recently attracted great attention for glioblastoma chemotherapy. One of the early benefits of combination therapies is the high potential to provide synergistic effects and decrease adverse side effects associated with high doses of single anticancer drugs. Therefore, brain tumor treatments with combination drugs can be considered as a crucial approach for avoiding tumor growth. This review investigates current progress in nano-mediated co-delivery of therapeutic agents with focus on glioblastoma chemotherapy prognosis.

The nanofibrous PAN-PANi scaffold as an efficient substrate for skeletal muscle differentiation using satellite cells.

Among polymers, polyaniline (PANi) has been introduced as a good candidate for muscle regeneration due to high conductivity and also biocompatibility. Herein, for the first time, we report the use of electrospun nanofibrous membrane of PAN-PANi as efficient scaffold for muscle regeneration. The prepared PAN-PANi electrospun nanofibrous membrane was characterized by scanning electron microscopy (SEM), Attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR) and tensile examination. The softer scaffolds of non-composite electrospun nanofibrous PAN govern a higher rate of cell growth in spite of lower differentiation value. On the other hand, PAN-PANi electrospun nanofibrous membrane exposed high cell proliferation and also differentiation value. Thank to the conductive property and higher Young's modulus of composite type due to the employment of PANi, satellite cells were induced into more matured form as analyzed by Real-Time PCR. On the other hand, grafting of composite nanofibrous electrospun scaffold with gelatin increased the surface stiffness directing satellite cells into lower cell proliferation and highest value of differentiation. Our results for first time showed the significant role of combination between conductivity, mechanical property and surface modification of PAN-PANi electrospun nanofibers and provid new insights into most biocompatible scaffolds for muscle tissue engineering. The schematic figure conveys the effective combination of conductive and surface stiffness on muscle tissue engineering.

Performance of electrodes synthesized with polyacrylonitrile-based carbon nanofibers for application in electrochemical sensors and biosensors.

The purpose of this work was to investigate the performance of electrodes synthesized with Polyacrylonitrile-based carbon nanofibers (PAN-based CNFs). The homogenous PAN solutions with different concentrations were prepared and electrospun to acquire PAN nanofibers and then CNFs were fabricated by heat treatment. The effective parameters for the production of electrospun CNF electrode were investigated. Scanning electron microscopy (SEM) was used to characterize electrospun nanofibers. Cyclic voltammetry was applied to investigate the changes of behavior of electrospun CNF electrodes with different diameters. The structure of CNFs was also evaluated via X-ray diffraction (XRD) and Raman spectroscopy. The results exhibited that diameter of nanofibers reduced with decreasing polymer concentration and applied voltage and increasing tip-to-collector distance, while feeding rate did not have significant effect on nanofiber diameter. The investigations of electrochemical behavior also demonstrated that cyclic voltammetric response improved as diameter of CNFs electrode decreased.

Electrochemical DNA biosensor based on gold nanorods for detecting hepatitis B virus.

The purpose of this work was to fabricate an electrochemical DNA biosensor for detecting hepatitis B virus. Gold nanorods (GNRs), which are known for their conductivity, were used to increase surface area and consequently increase the immobilization of single-stranded DNA (ss-DNA) on the modified gold electrode. The GNRs were characterized via transmission electron microscopy. The morphology of the gold electrode before and after modification with GNRs was characterized by scanning electron microscopy. Atomic-force microscopy was used to evaluate the morphology of the GNR electrode surface before and after interaction with ss-DNA. Cyclic voltammetry was used to monitor DNA immobilization and hybridization, using [Co(phen)3](3+) as an electrochemical indicator. The target DNA sequences were quantified at a linear range from 1.0 × 10(-12) to 10.0 × 10(-6) mol L(-1), with a detection limit of 2.0 × 10(-12) mol L(-1) by 3σ. The biosensor had good specificity for distinguishing complementary DNA in the presence of non-complementary and mismatched DNA sequences.