The death ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF cytokine superfamily, has long been recognized for its potential as a cancer therapeutic ...due to its low toxicity against normal cells. However, its translation into a therapeutic molecule has not been successful to date, due to its short in vivo half-life associated with insufficient tumor accumulation and resistance of tumor cells to TRAIL-induced killing. Nanotechnology has the capacity to offer solutions to these limitations. This review provides a perspective and a critical assessment of the most promising approaches to realize TRAIL’s potential as an anticancer therapeutic, including the development of fusion constructs, encapsulation, nanoparticle functionalization and tumor-targeting, and discusses the current challenges and future perspectives.
Immunosensors based on interdigitated electrodes (IDEs), have recently demonstrated significant improvements in the sensitivity of capacitance detection. Herein, a novel type of highly sensitive, ...compact and portable immunosensor based on a gold interdigital capacitor has been designed and developed for the rapid detection of hepatitis B surface antigen (HBsAg). To improve the efficiency of antibody immobilization and time-saving, a self-assembled monolayer (SAM) of 2-mercaptoethylamine film was coated on IDEs. Afterwards, carboxyl groups on primary antibodies were activated through 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and were immobilized on amino-terminated SAM for better control of the oriented immobilization of antibodies on gold IDEs. In addition, gold nanoparticles conjugated with a secondary antibody were used to enhance the sensitivity. Under optimal conditions, the immunosensor exhibited the sensitivity of 0.22 nF.pg ml-1, the linear range from 5 pg ml−1 to 1 ng ml-1 and the detection limit of 1.34 pg ml−1, at a signal-to-noise ratio of 3.
In this study, a novel method to probe molecular interactions and binding of human hemoglobin (Hb) with nanodiamond (ND) was introduced based on the surface tension measurement. This method ...complements conventional techniques, which are basically done by zeta potential and dynamic light scattering (DLS) measurements, near and far circular dichroism (CD) spectroscopy, intrinsic and extrinsic fluorescence spectroscopy. Addition of ND to Hb solution increased the surface tension value of Hb-ND complex relative to those of Hb and ND molecules. The zeta potential values reveled that Hb and ND provide identical charge distribution at pH 7.5. DLS measurements demonstrated that Hb, ND, and ND-Hb complex have hydrodynamic radiuses of 98.37 ± 4.57, 122.07 ± 7.88 nm and 62.27 ± 3.70 at pH of 7.5 respectively. Far and near UV-CD results indicated the loss of α-helix structure and conformational changes of Hb, respectively. Intrinsic fluorescence data demonstrated that the fluorescence quenching of Hb by ND was the result of the static quenching. The hydrophobic interaction plays a pivotal role in the interaction of ND with Hb. Fluorescence intensity changes over time revealed conformational change of Hb continues after the mixing of the components (Hb-ND) till 15 min, which is indicative of the denaturation of the Hb relative to the protein control. Extrinsic fluorescence data showed a considerable enhancement of the ANS fluorescence intensity of Hb-ND system relative to the Hb till 60 nM of ND, likely persuaded by greater exposure of nonpolar residues of Hb hydrophobic pocket. The remarkable decrease in T
m
value of Hb in Hb-ND complex exhibits interaction of Hb with ND conducts to conformational changes of Hb. This study offers consequential discrimination into the interaction of ND with proteins, which may be of significance for further appeal of these nanoparticles in biotechnology prosecution.
Herein, the interaction of hen egg white lysozyme (HEWL) with iron nanoparticle (Fe NP) was investigated by spectroscopic and docking studies. The zeta potential analysis revealed that addition of Fe ...NP (6.45±1.03 mV) to HEWL (8.57±0.54 mV) can cause to greater charge distribution of nanoparticle-protein system (17.33±1.84 mV). In addition, dynamic light scattering (DLS) study revealed that addition of Fe NP (92.95±6.11 nm) to HEWL (2.68±0.37 nm) increases suspension potential of protein/nanoparticle system (51.17±3.19 nm). Fluorescence quenching studies reveled that both static and dynamic quenching mechanism occur and hydrogen bond and van der Waals interaction give rise to protein-NP system. Synchronous fluorescence spectroscopy of HEWL in the presence of Fe NP showed that the emission maximum wavelength of tryptophan (Trp) residues undergoes a red-shift. ANS fluorescence data indicated a dramatic exposure of hydrophobic residues to the solvent. The considerable reduction in melting temperature (T(m)) of HEWL after addition of Fe NP determines an unfavorable interaction system. Furthermore circular dichoroism (CD) experiments demonstrated that, the secondary structure of HEWL has not changed with increasing Fe NP concentrations; however, some conformational changes occur in tertiary structure of HEWL. Moreover, protein-ligand docking study confirmed that the Fe NP forms hydrogen bond contacts with HEWL.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Herein, the interaction of iron nanoparticle (Fe-NP) with cytochrome c (Cyt c) was investigated, and a range of techniques such as dynamic light scattering (DLS), zeta potential measurements, static ...and synchronous fluorescence spectroscopy, near and far circular dichroism (CD) spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy were used to analyze the interaction between Cyt c and Fe-NP. DLS and zeta potential measurements showed that the values of hydrodynamic radius and charge distribution of Fe-NP are 83.95 ± 3.7 nm and 4.5 ± .8 mV, respectively. The fluorescence spectroscopy results demonstrated that the binding of Fe-NP with Cyt c is mediated by hydrogen bonds and van der Waals interactions. Also Fe-NP induced conformational changes in Cyt c and reduced the melting temperature value of Cyt c from 79.18 to 71.33°C. CD experiments of interaction between Fe-NP and Cyt c revealed that the secondary structure of Cyt c with the dominant α-helix structures remained unchanged whereas the tertiary structure and heme position of Cyt c are subjected to remarkable changes. Absorption spectroscopy at 695 nm revealed that Fe-NP considerably disrupt the Fe...S(Met80) bond. In addition, the UV-vis experiment showed the peroxidase-like activity of Cyt c upon interaction with Fe-NP. Hence, the data indicate the Fe-NP results in unfolding of Cyt c and subsequent peroxidase-like activity of denatured species. It was concluded that a comprehensive study of the interaction of Fe-NP with biological system is a crucial step for their potential application as intracellular delivery carriers and medicinal agents.
Hematopoietic stem cells (HSC) are responsible for the production of mature blood cells. To ensure that the HSC pool does not get exhausted over the lifetime of an individual, most HSCs are in a ...state of quiescence with only a small proportion of HSCs dividing at any one time. HSC quiescence is carefully controlled by both intrinsic and extrinsic, niche-driven mechanisms. In acute myeloid leukemia (AML), the leukemic cells overtake the hematopoietic bone marrow niche where they acquire a quiescent state. These dormant AML cells are resistant to chemotherapeutics. Because they can re-establish the disease after therapy, they are often termed as quiescent leukemic stem cells (LSC) or leukemia-initiating cells. While advancements are being made to target particular driver mutations in AML, there is less focus on how to tackle the drug resistance of quiescent LSCs. This review summarises the current knowledge on the biochemical characteristics of quiescent HSCs and LSCs, the intracellular signaling pathways and the niche-driven mechanisms that control quiescence and the key differences between HSC- and LSC-quiescence that may be exploited for therapy.
Despite the promising medicinal properties, berberine (BBR), due to its relatively poor solubility in plasma, low bio-stability and limited bioavailability is not used broadly in clinical stages. Due ...to these drawbacks, drug delivery systems (DDSs) based on nanoscale natural polysaccharides, are applied to address these concerns. Natural polymers are biodegradable, non-immunogenic, biocompatible, and non-toxic agents that are capable of trapping large amounts of hydrophobic compounds in relatively small volumes. The use of nanoscale natural polysaccharide improves the stability and pharmacokinetics of the small molecules and, consequently, increases the therapeutic effects and reduces the side effects of the small molecules. Therefore, this paper presents an overview of the different methods used for increasing the BBR solubility and bioavailability. Afterwards, the pharmacodynamic and pharmacokinetic of BBR nanostructures were discussed followed by the introduction of natural polysaccharides of plant (cyclodextrines, glucomannan), the shells of crustaceans (chitosan), and the cell wall of brown marine algae (alginate)-based origins used to improve the dissolution rate of poorly soluble BBR and their anticancer and antibacterial properties. Finally, the anticancer and antibacterial mechanisms of free BBR and BBR nanostructures were surveyed. In conclusion, this review may pave the way for providing some useful data in the development of BBR-based platforms for clinical applications.
Giant Unilamellar Vesicles
In article number 2302461, Jorik Waeterschoot, Xavier Casadevall i Solvas, and co‐workers present a new technique that harnesses the stabilization of microdroplets with ...silica nanoparticles for templating the formation of giant unilamellar vesicles (GUVs) integrating conformationally‐correct transmembrane proteins. Resulting GUVs could easily be released by centrifugation adding a new resource to the toolbox of the artificial cell community.
In the quest to produce artificial cells, one key challenge that remains to be solved is the recreation of a complex cellular membrane. Among the existing models, giant unilamellar vesicles (GUVs) ...are particularly interesting due to their intrinsic compartmentalisation ability and their resemblance in size and shape to eukaryotic cells. Many techniques have been developed to produce GUVs all having inherent advantages and disadvantages. Here, the authors show that fluorinated silica nanoparticles (FNPs) used to form Pickering emulsions in a fluorinated oil can destabilise lipid nanosystems to template the formation of GUVs. This technique enables GUV production across a broad spectrum of buffer conditions, while preventing the leakage of the encapsulated components into the oil phase. Furthermore, a simple centrifugation process is sufficient for the release of the emulsion‐trapped GUVs, bypassing the need to use emulsion‐destabilising chemicals. With fluorescent FNPs and transmission electron microscopy, the authors confirm that FNPs are efficiently removed, producing contaminant‐free GUVs. Further experiments assessing the lateral diffusion of lipids and unilamellarity of the GUVs demonstrate that they are comparable to GUVs produced via electroformation. Finally, the ability of incorporating transmembrane proteins is demonstrated, highlighting the potential of this method for the production of GUVs for artificial cell applications.
A novel method for the production of giant unilamellar vesicles (GUVs) is presented. Here, partially fluorinated silica nanoparticles are utilized for the stabilization of a lipid‐containing aqueous droplet in a fluorinated oil. The encapsulated lipids assemble at the droplet interface forming a GUV, which can be released in an outer aqueous medium by centrifugation.
Subtle changes in the structure of nanoparticles influence their surface tension and corresponding interaction with cells and proteins. Here, the interaction of the single wall carbon nanotube ...(SWCNT) and multiwall carbon nanotube (MWCNT) with different surface tension with tau protein was evaluated using a variety of techniques including far and near circular dichroism, fluorescence spectroscopy, dynamic light scattering, Zeta potential, and TEM evaluation. Also the cytotoxicity of SWCNT and MWCNT on the PC12 cell line as a model of nervous system cell line was investigated by the MTT, LDH, acridine orange/ethidium bromide staining, flow cytometry, caspase 3 activity, cell and membrane potential assays. It was observed that SWCNT induced more structural changes of tau protein relative to MWCNT/tau protein interaction. It was also revealed that SWCNT and MWCNT impaired the viability and complexity of PC12 cells in different modes of cytotoxicity. Analysis of cellular outcomes indicated that MWCNT in comparison with SWCNT resulted in induction of necrotic modes of cell death, whereas apoptotic modes of cell death were activated in SWCNT-incubated cells. Together these findings suggest that surface tension may be used to determine how nanoparticle structure affects neurotoxicity and protein conformational changes.
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