Nanotechnology-Abetted Astaxanthin Formulations in Multimodel Therapeutic and Biomedical Applications.

Astaxanthin (AXT) is one of the most important fat-soluble carotenoids that have abundant and diverse therapeutic applications namely in liver disease, cardiovascular disease, cancer treatment, protection of the nervous system, protection of the skin and eyes against UV radiation, and boosting the immune system. However, due to its intrinsic reactivity, it is chemically unstable, and therefore, the design and production processes for this compound need to be precisely formulated. Nanoencapsulation is widely applied to protect AXT against degradation during digestion and storage, thus improving its physicochemical properties and therapeutic effects. Nanocarriers are delivery systems with many advantages─ease of surface modification, biocompatibility, and targeted drug delivery and release. This review discusses the technological advancement in nanocarriers for the delivery of AXT through the brain, eyes, and skin, with emphasis on the benefits, limitations, and efficiency in practice.

Controlled Gene Delivery Systems: Nanomaterials and Chemical Approaches.

Successful gene therapy depends on the design of effective gene delivery systems. A gene delivery system is considered a powerful tool for the release of genetic material within cells resulting in a change in cell functions and protein production. The release of genes in a controlled manner by using appropriate carriers facilitates their release without side effects and increases the expression of genes at the released site. It is expected that significant changes in the combination of several genes and drugs can be provided by developing treatment systems sensitive to different stimuli such as redox potential, pH variations, temperature gradients, light irradiation, and enzyme activity. The most important advantages for the release of genes and stimuli-responsive therapeutics include delivering vectors locally, reducing side effects and causing no toxicity to distant tissues while at the same time reducing the immune response to the vectors. In this review, we aim to discuss different types of gene carriers involved in the controlled transfer of nucleic acids (non-viral inorganic and organic nanoparticles (NPs) and virus-like particles (VLPs)) as well as the simultaneous transfer of several genes and/or drugs into cells or different tissues, providing for an efficient and safe treatment of numerous diseases.

Stimulus-Responsive Sequential Release Systems for Drug and Gene Delivery.

In recent years, a range of studies have been conducted with the aim to design and characterize delivery systems that are able to release multiple therapeutic agents in controlled and programmed temporal sequences, or with spatial resolution inside the body. This sequential release occurs in response to different stimuli, including changes in pH, redox potential, enzyme activity, temperature gradients, light irradiation, and by applying external magnetic and electrical fields. Sequential release (SR)-based delivery systems, are often based on a range of different micro- or nanocarriers and may offer a silver bullet in the battle against various diseases, such as cancer. Their distinctive characteristic is the ability to release one or more drugs (or release drugs along with genes) in a controlled sequence at different times or at different sites. This approach can lengthen gene expression periods, reduce the side effects of drugs, enhance the efficacy of drugs, and induce an anti-proliferative effect on cancer cells due to the synergistic effects of genes and drugs. The key objective of this review is to summarize recent progress in SR-based drug/gene delivery systems for cancer and other diseases.

Aptamer Hybrid Nanocomplexes as Targeting Components for Antibiotic/Gene Delivery Systems and Diagnostics: A Review.

With the passage of time and more advanced societies, there is a greater emergence and incidence of disease and necessity for improved treatments. In this respect, nowadays, aptamers, with their better efficiency at diagnosing and treating diseases than antibodies, are at the center of attention. Here, in this review, we first investigate aptamer function in various fields (such as the detection and remedy of pathogens, modification of nanoparticles, antibiotic delivery and gene delivery). Then, we present aptamer-conjugated nanocomplexes as the main and efficient factor in gene delivery. Finally, we focus on the targeted co-delivery of genes and drugs by nanocomplexes, as a new exciting approach for cancer treatment in the decades ahead to meet our growing societal needs.

The Pimpled Gold Nanosphere: A Superior Candidate for Plasmonic Photothermal Therapy.

BACKGROUND: The development of highly efficient nanoparticles to convert light to heat for anti-cancer applications is quite a challenging field of research. METHODS: In this study, we synthesized unique pimpled gold nanospheres (PGNSs) for plasmonic photothermal therapy (PPTT). The light-to-heat conversion capability of PGNSs and PPTT damage at the cellular level were investigated using a tissue phantom model. The ability of PGNSs to induce robust cellular damage was studied during cytotoxicity tests on colorectal adenocarcinoma (DLD-1) and fibroblast cell lines. Further, a numerical model of plasmonic (COMSOL Multiphysics) properties was used with the PPTT experimental assays. RESULTS: A low cytotoxic effect of thiolated polyethylene glycol (SH-PEG400-SH-) was observed which improved the biocompatibility of PGNSs to maintain 89.4% cell viability during cytometry assays (in terms of fibroblast cells for 24 hrs at a concentration of 300 µg/mL). The heat generated from the nanoparticle-mediated phantom models resulted in ΔT=30°C, ΔT=23.1°C and ΔT=21°C for the PGNSs, AuNRs, and AuNPs, respectively (at a 300 µg/mL concentration and for 325 sec). For the in vitro assays of PPTT on cancer cells, the PGNS group induced a 68.78% lethality (apoptosis) on DLD-1 cells. Fluorescence microscopy results showed the destruction of cell membranes and nuclei for the PPTT group. Experiments further revealed a penetration depth of sufficient PPTT damage in a physical tumor model after hematoxylin and eosin (H&E) staining through pathological studies (at depths of 2, 3 and 4 cm). Severe structural damages were observed in the tissue model through an 808-nm laser exposed to the PGNSs. CONCLUSION: Collectively, such results show much promise for the use of the present PGNSs and photothermal therapy for numerous anti-cancer applications.

Apelin attenuates streptozotocin-induced learning and memory impairment by modulating necroptosis signaling pathway.

Apelin is a neuropeptide that plays an important role in neuronal protection. In this study, we investigated the effects of apelin intracerebroventricular administration on spatial learning and memory-related behaviors, and necroptosis signaling pathways in the hippocampus of streptozotocin (STZ) -injected rats. Apelin treatment was implemented following STZ-induced dementia for 15 days. After conducting a behavioral test (Morris Water Maze), the cellular and molecular aspects were examined to detect the apelin effect on the necroptosis signaling pathway. We demonstrated that STZ administration significantly slowed down the learning capability. However apelin treatment notably reversed this neuroinflammation induced behavioral impairment. Furthermore, molecular investigations showed that apelin treatment reduced the hippocampal RIP1, RIP3, and TNF-α level. Our results suggest that apelin treatment attenuates STZ-induced dementia. This effect may be mediated by inhibition of the necroptosis signaling pathway which seems to be associated with the ability of apelin to reduce central TNF-α level. This data provides evidence of the neuroprotective effect of apelin on STZ-induced learning and memory impairment and characterize some of the underlying mechanisms.

Penetration Depth in Nanoparticles Incorporated Radiofrequency Hyperthermia into the Tissue: Comprehensive Study with Histology and Pathology Observations.

In present study, the effective penetration of radiofrequency (RF) induced gold decorated iron oxide nanoparticles (GS@IONPs) hyperthermia was investigated. The effective penetration depth of RF also the damage potency of hyperthermia was evaluated during histopathology observations which were done on the chicken breast tissue and hepatocellular carcinoma (HCC) models. The thermal damages are well- documented in our previous cellular study which was engaged with potency of RF hyperthermia in Epithelial adenocarcinoma (MCF-7) and fibroblast (L-929) cells deaths [1]. In recent work, PEGylated iron oxide nanoparticles (IONPs) were used as base platform for gold magnetic nanoparticles (GS@IONPs) formation. The 144.00015 MHz, 180W RF generator was applied for stimulating the nanoparticles. The chicken breast tissue and the hepatocellular tumor model was considered in the experimental section. In histology studies, the structural changes also the effective penetration depth of RF induced nanoparticles was observed through microscopic monitoring of the tissue slices in histology observations (Gazi medical school). The highest damage level was seen in 8.0 µm tissue slices where lower damages were seen in depth of 1.0 cm and more inside tissue. The histology observations clarified the effective penetration depth of RF waves and irreversible damages in the 2.0 cm inside the tissue.

Thymulin treatment attenuates inflammatory pain by modulating spinal cellular and molecular signaling pathways.

Thymulin is a peptide hormone which is mainly produced by thymic epithelial cells and it has immune-modulatory and anti-inflammatory effects. In this study, we investigated the effects of different doses and various timings of thymulin intraperitoneal administration on spinal microglial activity and intracellular pathways in an inflammatory rat model of Complete Freund's adjuvant (CFA). Thymulin treatment was implemented following CFA-induced inflammation for 21 days. After conducting behavioral tests (edema and hyperalgesia), the cellular and molecular aspects were examined to detect the thymulin effect on inflammatory factors and microglial activity. We demonstrated that thymulin treatment notably reduced thermal hyperalgesia and paw edema induced by CFA. Furthermore, molecular investigations showed that thymulin reduced CFA-induced activation of microglia cells, phosphorylation of p38 MAPK and the production of spinal pro-inflammatory cytokines (TNF-α, IL-6) during the study. Our results suggest that thymulin treatment attenuates CFA-induced inflammation. This effect may be mediated by inhibition of spinal microglia and production of central inflammatory mediators which seems to be associated with the ability of thymulin to reduce p38 MAPK phosphorylation. These data provide evidence of the anti-hyperalgesic effect of thymulin on inflammatory pain and characterize some of the underlying spinal mechanisms.

Electrospun essential oil-polycaprolactone nanofibers as antibiofilm surfaces against clinical Candida tropicalis isolates.

OBJECTIVE: As an approach to prevent biofilm infections caused by Candida tropicalis on various surfaces, determination of effect of biodegradable polycaprolactone nanofibers (PCLNFs) with different concentrations of two different essential oils were tested in this study. RESULTS: Both of the tested essential oils exhibited antifungal effect (minimal inhibitory concentration; 0.25-0.49 µL/mL, minimal fungicidal concentration; 0.25-0.49 µL/mL, depending on the C. tropicalis strain) (Zone of inhibition caused by 500 µL/mL concentration of oils; 28-56 mm). 0, 2, 4% clove oil PCLNFs and 0, 2, 4% red thyme oil-PCLNFs were free from bead formation and uniform in diameter. Diameters of all essential oil containing PCLNFs were ranged from 760 to 1100 nm and were significantly different from 0% essential oil-PCLNF (P < 0.05). 0, 2, 4% clove oil-PCLNFs were significantly more hydrophobic compared to 8% clove oil-PCLNF (P < 0.01), whereas 0% and 2% red thyme oil-PCLNFs were significantly more hydrophobic compared to 4% and 8% red thyme oil PCLNFs (P < 0.01). Highest amount of biofilm inhibition was observed by 4% clove oil-PCLNF and by 4% red thyme oil-PCLNF. CONCLUSIONS: Clove and red thyme oils may be used not only as antifungals but also as biofilm inhibitive agents on surfaces of biomaterials that are frequently contaminated by C. tropicalis, when they are incorporated into PCLNFs.

Time-course study of high fat diet induced alterations in spatial memory, hippocampal JNK, P38, ERK and Akt activity.

Consumption of high fat diet (HFD) is a health concern in modern societies, which participate in wide range of diseases. One underlying mechanism in the HFD mediated pathologies is disruption of insulin signaling activity. It is believed that HFD activates several stress signaling molecules such as MAPKs signaling pathway and these molecules participate in harmful effects in different cell populations including hippocampal cells. However, the activity of MAPKs signaling molecules are time dependent, even causing some opposing effects. Given that, MAPKs activity fluctuate with time of stress, there is less cleared how different lengths of HFD consumption can affect hippocampal MAPK. To test how duration of HFD consumption affect hippocampal MAPKs and insulin signaling activity and animal's cognitive function, rats were fed with HFD for different lengths (up to 6 months) and after each point spatial memory performances of animals was tested, then the peripheral indices of insulin resistance and hippocampal MAPKs and insulin signaling activity was evaluated. Results showed that while different time courses of HFD, up to 6 months, did not bring about significant spatial memory impairment, meanwhile the peripheral insulin sensitivity as well as hippocampal insulin and MAPKs signaling showed significant fluctuations during the different time courses of high fat diet regime. These results showed that neuronal responses to HFD is not constant and differ in a time-dependent manner, it seems that in acute phase molecular responses aimed to compensate the HFD stress but in chronic states these responses failed and devastating effects of stress began.

Point-of-care microfluidic devices for pathogen detection.

The rapid diagnosis of pathogens is crucial in the early stages of treatment of diseases where the choice of the correct drug can be critical. Although conventional cell culture-based techniques have been widely utilized in clinical applications, newly introduced optical-based, microfluidic chips are becoming attractive. The advantages of the novel methods compared to the conventional techniques comprise more rapid diagnosis, lower consumption of patient sample and valuable reagents, easy application, and high reproducibility in the detection of pathogens. The miniaturized channels used in microfluidic systems simulate interactions between cells and reagents in microchannel structures, and evaluate the interactions between biological moieties to enable diagnosis of microorganisms. The overarching goal of this review is to provide a summary of the development of microfluidic biochips and to comprehensively discuss different applications of microfluidic biochips in the detection of pathogens. New types of microfluidic systems and novel techniques for viral pathogen detection (e.g. HIV, HVB, ZIKV) are covered. Next generation techniques relying on high sensitivity, specificity, lower consumption of precious reagents, suggest that rapid generation of results can be achieved via optical based detection of bacterial cells. The introduction of smartphones to replace microscope based observation has substantially improved cell detection, and allows facile data processing and transfer for presentation purposes.

Optical assays based on colloidal inorganic nanoparticles.

Colloidal inorganic nanoparticles have wide applications in the detection of analytes and in biological assays. A large number of these assays rely on the ability of gold nanoparticles (AuNPs, in the 20 nm diameter size range) to undergo a color change from red to blue upon aggregation. AuNP assays can be based on cross-linking, non-cross linking or unmodified charge-based aggregation. Nucleic acid-based probes, monoclonal antibodies, and molecular-affinity agents can be attached by covalent or non-covalent means. Surface plasmon resonance and SERS techniques can be utilized. Silver NPs also have attractive optical properties (higher extinction coefficient). Combinations of AuNPs and AgNPs in nanocomposites can have additional advantages. Magnetic NPs and ZnO, TiO2 and ZnS as well as insulator NPs including SiO2 can be employed in colorimetric assays, and some can act as peroxidase mimics in catalytic applications. This review covers the synthesis and stabilization of inorganic NPs and their diverse applications in colorimetric and optical assays for analytes related to environmental contamination (metal ions and pesticides), and for early diagnosis and monitoring of diseases, using medically important biomarkers.

Anti-biofilm effect of nanometer scale silver (NmSAg) coatings on glass and polystyrene surfaces against P. mirabilis, C. glabrata and C. tropicalis strains.

PURPOSE: Nowadays, in order to terminate biofilm associated infections, coating of particular biomaterial surfaces with particular substances, via some nanotechnological tools, is being applied. Therefore, in the present study, investigation of anti-biofilm effects of nanometer scale silver (NmSAg) coatings on glass and polystyrene surfaces against clinical strains of Proteus mirabilis, Candida glabrata and Candida tropicalis was aimed. METHODS: In this study, glass and polystyrene slabs with 1.5 cm × 1.5 cm × 0.3 mm dimensions were cleaned by using surface plasma technology, covered with NmSAg by using a physical vapor deposition machine, and biofilm inhibition was determined by crystal violet binding assay. RESULTS: According to our results, 32 nm of silver layer on a glass slab decreased biofilm formation of P. mirabilis strain to a maximum amount of 88.1% and caused 20.9% inhibition in biofilm formation of C. glabrata strain. On the other hand, NmS coating of Ag on a polystyrene slab caused 34.4% and 20% inhibitions, respectively, in biofilm formations of C. glabrata and C. tropicalis strains. Although biofilm inhibition of NmSAg layer on polystyrene slab was more (34.4%) than biofilm inhibition caused by NmSAg layer on glass slab (20.9%), C. glabrata strain's biofilm formation on uncoated glass slab was lower than both uncoated and NmSAg-coated polystyrene slabs. CONCLUSIONS: Our results show that glass surfaces with NmSAg coatings can be used as a new surface material of various indwelling devices on which P. mirabilis colonizations frequently occur and in order to avoid C. glabrata-associated biofilm infections, it is more useful to choose a surface material of glass rather than choosing a surface material of polystyrene.