Alzheimer's disease (AD) constitutes a complex pathological process and ranks among the leading causes of dementia globally. There is an escalating demand for diagnostic tools that are minimally invasive, timely, and accurate. The total Tau (T-Tau) protein in blood serum has emerged as a promising biomarker for the early diagnosis of AD. In this study, a magnetic hexagonal boron nitride (MHBN)-based immunosensor platform was developed to detect T-Tau in artificial blood serum. Following the exfoliation of hexagonal boron nitride (HBN), magnetite nanoparticles were deposited onto the surface of the HBN nanosheets, followed by (3-Aminopropyl) triethoxysilane (APTES) modification. The resulting MHBN-APTES nanocomposite-modified screen-printed carbon electrode acted as a matrix for immobilizing Anti-T-Tau antibodies. The analytical performance of the MHBN-APTES/Anti-T-Tau immunosensor in the presence of T-Tau isoforms was evaluated using cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy techniques. The linear detection range was established at 0.5-50 pg/mL, with a limit of detection of 0.39 pg/mL for T-Tau, which is appropriate for identifying T-Tau in blood serum. The MHBN-APTES/Anti-T-Tau also demonstrated good repeatability, reproducibility, and stability, making it a dependable option for advanced applications.
The improvement of surface treatment methods that permit the tuning of cell adhesion on the surface of biomaterials and devices is of considerable importance. Here, multi-walled carbon nanotubes (MWCNT) were modified with 4-aminothiophenol (4ATP). Then, electrodeposition of MWCNT-4ATP was carried out on 4ATPmodified screen-printed gold electrodes (SP-Au). After conjugation of Arginyl-glycyl-aspartic acid (RGD)-pep- tide on Poly(MWCNT-4ATP), the adhesion of U-87MG glioblastoma cells was examined by differential pulse voltammetry (DPV) technique. The synthesized MWCNT-4ATP and the obtained Poly(MWCNT-4ATP)/RGD surfaces were characterized using Scanning Electron Microscopy-Energy Dispersive X-Ray Spectrometer (SEMEDS), Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), X-Ray Photoelectron Spectrometer (XPS). The linear range for U-87MG glioblastoma cells was 102-106 cells/mL. The developed Poly (MWCNT-4ATP)/RGD cell adhesion platform provided monitoring of U-87MG glioblastoma cells using DPV technique and fluorescent imaging.
The relationship between biological materials and the immobilization matrix is a critical point in attaching biomolecules onto transducers in the preparation of biosensors. Various chemical molecules are used to conjugate biological compounds in the design of biofunctional surfaces. Among them, chemobrionics (CBCs) are good alternatives as an immobilization matrix to improve performance parameters such as linear range, limit of detection (LOD), stability, reproducibility, etc. Here, CBCs are used to develop enzymatic biosensor, and glucose oxidase (GOx) is selected as a model enzyme. Firstly, CBC is functionalized using (3-Aminopropyl)triethoxysilane (APTES) to obtain free amine groups for immobilization of GOx via covalent bonds. The synthesized CBC-APTES is used as a matrix for the conjugation of GOx using glutaraldehyde as a crosslinker. The proposed CBC-APTES/ GOx is formed on the glassy carbon electrode, and its performance is checked for glucose detection. The linear range is 0.025-1.25 mM with an LOD of 0.024 mM glucose. After finding no effect of some potential interference on the current response, CBC-APTES/GOx is successfully applied to analyze glucose in artificial samples such as serum, urine, sweat, and saliva. The objective here is to outline the integration of CBC in biosensor preparation, which has been successfully carried out for the first time in the literature.
In recent years, the rapid development of nanotechnology has caused the products obtained with this technology to be used more daily. Information on the effects of these products, which provide great advantages in every respect, on human health and the environment is insufficient. It has been suggested that these nanoparticles may have toxic effects on living things, mostly in animal experiments and cell cultures. In this paper, the organism Caenorhabditis elegans (C. elegans), which contains a genome and biochemical ways highly similar to humans, is used to understand and reveal the metabolism of Zinc oxide nanoparticles (ZnO NPs) toxicological effects. The toxicological effects of ZnO NPs on C. elegans organisms were investigated and the results were evaluated in terms of environment and human health. C. elegans was exposed to commercial ZnO NPs and green synthesized ZnO NPs from Olea europaea (olive tree, OLE). LC50 values were determined by probit analysis (green synthesized ZnO NP LC5024h = 84.97 mg/L, LC5072h = 33.27 mg/L, commercial ZnO NPs LC5024h = 5.75 mg/L, LC5072h = 1.91 mg/L). When the survival times of C. elegans were evaluated by the Kaplan–Meier method, it was seen that commercial ZnO NPs were more toxic than green synthesized ZnO NPs. In MTT tests, it was clearly seen that commercial ZnO NPs and green synthesized ZnO NPs entered the cell and caused different cytotoxicity. While there was a difference between control and 0.5, 2.5, 5, 10, 25, and 50 mg/L doses in commercial ZnO NP applications, there were significant differences between control and 25, 50 mg/L concentrations in green synthesized ZnO NP applications.
Alzheimer's disease (AD) is a complex pathological process that is one of the leading causes of dementia globally. The demand for diagnostic tools that are minimally invasive, timely, and accurate is on the rise. Total tau (T-Tau) protein in blood serum is a promising biomarker for predicting early-stage AD diagnosis. In this study, the hexagonal boron nitride (HBN) based immunosensor platform was developed to detect T-Tau in artificial blood serum. After the exfoliation of HBN, its surface was coated with polydopamine (PDA) in alkaline conditions. The Anti-T-Tau was immobilized on a hydrophilic nanocomposite surface using PDA's reactive catechol and quinone groups, eliminating the need for extra crosslinkers. The working electrode surface of the screen-printed carbon electrode (SPCE) was coated with HBN-PDA nanocomposite using the drop-casting method. The biofunctional surface was created by directly immobilizing Anti-T-Tau on the HBN-PDA nanocomposite-modified SPCE. The analytical performance of the HBN-PDA/Anti-T-Tau/T-Tau immunosensor in the presence of T-Tau isoforms was determined through electrochemical measurements. The linear detection range was 1-30 pg/mL with a detection limit of 0.42 pg/mL for T-Tau, which is suitable for detecting T-Tau in the blood serum.
Nanomaterials have revolutionized scientific research due to their exceptional physical and chemical capabilities. Carbon-based nanomaterials such as graphene and its derivates have excellent electrical, optical, thermal, physical, and chemical properties that have made them indispensable in several industries worldwide, including medicine, electronics, and energy. By incorporating carbon-based nanomaterials as nanofillers in electrospun nanofibers (ESNFs), smoother and highly conductive nanofibers can be achieved that possess a large surface area and porosity. This approach provides a superior alternative to traditional materials in the development of improved biosensors. Carbon-based ESNFs, among the most exciting new-generation materials, have many applications, including filtration, pharmaceuticals, biosensors, and membranes. The electrospinning technique is a highly efficient and cost-effective method for producing desired nanofibers compared to other methods. Various types of natural and synthetic organic polymers have been successfully utilized in solution electrospinning to produce nanofibers directly. To create diagnostics devices, various biomolecules like antibodies, enzymes, aptamers, ligands, and even cells can be bound to the surface of nanofibers. Electrospun nanofibers can serve as an immobilization matrix to create a biofunctional surface. Thus, biosensors with desired features can be produced in this way. This study comprehensively reviews biosensors that integrate nanodiamonds, fullerenes, carbon nanotubes, graphene oxide, and carbon dots into electrospun nanofibers.
The increased serum concentration of CD36 is significantly associated with atherosclerosis, insulin resistance, and diabetes mellitus. Currently, there is no sensor system used for the detection of CD36 in the clinical field. Therefore, there is a need to develop a sensor system for the detection of CD36. The large surface area/volume ratio and controllable surface conformation of electrospun nanofibers (ENs) make them highly attractive for immunosensor applications. In the present study, PS/MWCNT-PAMAM ENs were produced and used as an immobilization matrix of Anti-CD36. Thus, the electrochemical behavior of the developed nanocomposite-based ENs and their usage potential were investigated for immunosensor applications. First, an oxidized multiwall carbon nanotube (MWCNT-OH) was synthesized and modified with a polyamidoamine generation 3 (PAMAM G3) dendrimer. The synthesized MWCNT-PAMAM nanocomposite was mixed with polystyrene (PS) solutions at different ratios to produce bead-free, smooth, and uniform PS/MWCNT-PAMAM ENs. PS/MWCNT-PAMAM ENs were accumulated on a screen-printed carbon electrode (SPCE) using the electrospinning technique. A biofunctional surface on the PS/MWCNT-PAMAM EN-coated SPCE was created using carbodiimide chemistry by covalent immobilization of Anti-CD36. The analytic performance characteristics of the developed PS/MWCNT-PAMAM/Anti-CD36 immunosensor were determined by performing electrochemical measurements in the presence of the CD36 protein. The linear detection range was found to be from 5 to 40 ng/mL, and the limit of detection was calculated as 3.94 ng/mL for CD36. The developed PS/MWCNT-PAMAM/Anti-CD36 immunosensor also displayed high tolerance to interference substances, good repeatability, and high recovery percent (recovery%) for artificial blood serum analysis.
Introduction Apoptosis, necrosis, and cancer necrosis factor (TNF-a) are all impacted by the nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) at nano-biointerfaces. The creation of multi-functional nanoparticles has had a considerable impact on the transport of drugs and genes, nanotheranostics (in-vivo imaging, concurrent diagnostics), interventions for external healing, the creation of nano-bio interfaces, and the instigation of desired changes in nanotherapeutics. Objectives The quantitative structure-activity relationships, chemical transformations, biological interactions as well as toxicological analyses are considered as main objectives. Discrete dimensions of SCoNPs-cell interaction interfaces, their characteristic physical features (size, shape, shell structure, and surface chemistry), impact on cell proliferation and differentiation are the key factors responsible for nanotoxicity. Methods The development of multi-functional nanoparticles has been significant in drug/gene delivery, nanotheranostics (in-vivo imaging, coinciding diagnostics), and external healing interventions, designing a nano-bio interface, as well as inciting desired alterations in nanotherapeutics. Every so often, the cellular uptake of multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoONPs) influences cellular mechanics and initiates numerous repercussions (oxidative stress, DNA damage, cytogenotoxicity, and chromosomal damage) in pathways, including the generation of dysregulating factors involved in biochemical transformations. Results The concerns and influences of multifunctional SCoNPs on different cell mechanisms (mitochondria impermeability, hydrolysis of ATP, the concentration of Ca2+, impaired calcium clearance, defective autophagy, apoptosis, and necrosis), and interlinked properties (adhesion, motility, and internalization dynamics, role in toxicity, surface hydrophilic and hydrophobicity, biokinetics and biomimetic behaviors of biochemical reactions) have also been summarized. SCoONPs have received a lot of interest among the nanocarriers family because of its advantageous qualities such as biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity. Conclusion Various applications, such as bio-imaging, cell labeling, gene delivery, enhanced chemical stability, and increased biocompatibility, concerning apoptosis, necrosis, and nano-bio interfaces, along with suitable examples. In this analysis, the multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoNPs) intricacies (cytogenotoxicity, clastogenicity, and immunomodulatory), nanotoxicity, and associated repercussions have been highlighted and explained.
Nanoparticles are currently used for cancer theranostics in the clinical field. Among nanoparticles, gold nanoparticles (AuNPs) attract much attention due to their usability and high performance in imaging techniques. The wide availability of biological precursors used in plant-based synthesized AuNPs allows for the development of large-scale production in a greener manner. Conventional cancer therapies, such as surgery and chemotherapy, have significant limitations and frequently fail to produce satisfying results. AuNPs have a prolonged circulation time, allow easy modification with ligands detected via cancer cell surface receptors, and increase uptake through receptor-mediated endocytosis. To exploit these unique features, studies have been carried out on the use of AuNPs as contrast agents for X-ray-based imaging techniques (i.e., computed tomography). As nanocarriers, AuNPs synthesized by nontoxic and biocompatible plants to deliver therapeutic biomolecules could be a significant stride forward in the effective treatment of various cancers. Fluorescent-plant-based markers, including AuNPs, fabricated using Medicago sativa, Olax Scandens, H. ambavilla, and H. lanceolatum, have been used in detecting cancers. Moreover, green synthesized AuNPs using various extracts have been applied for the treatment of different types of solid tumors. However, the cytotoxicity of AuNPs primarily depends on their size, surface reactivity, and surface area. In this review, the benefits of plant-based materials in cancer therapy are firstly explained. Then, considering the valuable position of AuNPs in medicine, the application of AuNPs in cancer therapy and detection is highlighted with an emphasis on limitations faced by the application of such NPs in drug delivery platforms.
Aptamers are single-stranded oligonucleotides that link to various substrates with great affinity and selectivity, including small molecules, peptides, proteins, cells, and tissues. For this reason, they can be used as imaging agents for cancer imaging techniques. Multifunctional nanomaterials combined with imaging probes and drugs are promising cancer diagnosis and treatment candidates. On the other hand, carbon-based nanomaterials (CNMs), including such as fullerene, carbon nanotubes, carbon-based quantum dots, carbon nanohorns, graphene oxide and its derivatives carbon nanodots, and nanodiamonds, are sort of smart materials that can be used in a variety of theranostic applications, including photo-triggered therapies. The remarkable physical characteristics, functionalizable chemistry, biocompatibility, and optical properties of these nanoparticles have enabled their utilization in less-invasive therapies. The theranostic agents that emerged by combining aptamers with CNMs have opened a novel alternative for personified medicine of cancer, target-specific imaging, and label-free diagnosis of a broad range of cancers, as well as pathogens. Aptamer-functionalized CNMs have been used as nanovesicles for targeted delivery of anti-cancer agents (i.e., doxorubicin and 5-fluorouracil) to tumor sites. Furthermore, these CNMs conjugated with aptamers have shown great advantages over standard CNMs to sensitively detect Mycobacterium tuberculosis, Escherichia coli, staphylococcus aureus, Vibrio parahaemolyticus, Salmonella typhimurium, Pseudomonas aeruginosa, and Citrobacter freundii. Regrettably, CNMs can form compounds defined as NOAA (nano-objects, and their aggregates and agglomerates larger than 100 nm), that accumulate in the body and cause toxic effects. Surface modification and pretreatment with albumin avoid agglomeration and increase the dispersibility of CNMs, so it is needed to guarantee the desirable interactions between functionalized CNMs and blood plasma proteins. This preliminary review aimed to comprehensively discuss the features and uses of aptamer-conjugated CNMs to manage cancer and bacterial infections.
Electrospun nanofibers (ESNF) offer us a chance to obtain nanoscale building blocks by adding the desired modification agent to the polymer solution. Here, nanocomposite-based electrospun nanofibers designed for the recognition surface of the developed immunosensor were used for the first time in the determination of CD36. Firstly, graphene oxide (GO) was synthesized from graphite powder (GR), and GO sheets were silanized with different amounts of (3-Aminopropyl)triethoxysilane (APTES). Synthesized GO-APTES nanocomposite and polystyrene (PS) solution were mixed in different ratios to obtain uniform nanofibers without beads. As a result of the amino groups obtained on the surface of the nanofibers, the surface was made ready for covalent immobilization of the Anti-CD36 antibody. The nanofibers obtained under the optimum conditions determined were deposited on the surface of the screen-printed carbon electrode (SPCE) by the electrospinning technique. Then, Anti-CD36 was immobilized on the PS/GO-APTES modified SPCE through covalent bonding and used to prepare the biofunctional surface for the usage of bioelectrochemistry of CD36. The optimum Anti-CD36 con-centration decided to be used in experiments was determined as 10 mu g/mL. The linear detection range of CD36 was from 0.5 to 20 ng/mL, and the detection limit was 0.999 ng/mL. Finally, the developed PS/GO-APTES/Anti-CD36 immunosensor was used for the determination of CD36 in artificial blood serum without any interference effect.
Glioblastoma multiforme (GBM) is considered the most aggressive and heterogeneous type of brain malignancy. The substantial invasion of the central nervous system parenchyma is a typical hallmark of all grades of glioma. To improve tumor localization and prevent unanticipated toxicity, anti-tumor drug delivery mechanisms must be upgraded in parallel with pharmacotherapeutics. Monocytes can easily pass the blood-brain barrier, and thus, drugs with difficulty entering the brain can be loaded into monocytes, resulting in the treatment of brain cancers. RNA as a natural and biocompatible polymer has many advantages for biomedical applications, and RNA-based therapies can provide regulated biological functions by highly selective and controlling means. In this context, macrophages are excellent carriers for distributing RNA-based treatments. However, developing an efficient macrophage-targeted RNA delivery has remained challenging. Several approaches have been introduced in the last decade to efficiently deliver RNA-based therapy via macrophages to treat GBM and inflammatory conditions. This review summarizes the most suitable nano-carrier systems to deliver RNA into immunocytes; also, different methods of synthesizing RNA-loaded nanoparticles and their application, with an emphasis on targeting GBM, are discussed. Furthermore, it focuses specifically on the stability of such nanoformulations and the effect of targeting moieties and adjuvants in determining the worth of the aroused immune response. Finally, the critical aspects of delivering RNA-lipid hybrid nanoparticles (LNPs) via oral, systemic, and local routes are highlighted. We hope that these findings will pave the way for more effective treatment of solid tumors, such as GBM, in the future.
The usage of nanoparticles (NPs) in treating and diagnosing many diseases, especially cancer, has been investigated in recent studies. The primary purpose of using nanotechnology in cancer treatment is to design a specific NPs-based drug delivery system to target cells. Thanks to their slow degradation, controlled release, optimum surface functionaity, and high optical absorbance, NPs can be used as agents for photothermal therapy (PTT) and photodynamic therapy (PDT). In this connection, the efficiency of the treatment increases, and the side effects are reduced. Titanium dioxide (TiO2) is one of the most basic materials in daily life that represents tremendous photocatalyst activity. Recently, several functionalized biodegradable polymers were recently designed for TiO2 NP-based photothermal and photodynamic therapies. These photosensitizers can be modified by attaching dyes, targeting molecules, and drug molecules. Although these modifications resulted in and have shown enhanced water dispersibility and biocompatibility, TiO2 NPs possess the disadvantage of inducing oxidative stress, leading to the diminution of cellular antioxidants. The wide bandgap of TiO2 limits its absorption merely to the ultra-violet (UV) and not the NIR light region, which provides deep optical imaging of cancer tissue. In addition, the UV-stimulated TiO2 was successfully applied for phototherapy of skin cancers and yielded undesirable outcomes when applied to most deep-tissue tumors. This updated review contains numerous reports on the PDT and PTT applications of TiO2 NPs. More highly efficient functionalized biodegradable polymers exhibiting a non-toxic profile should be prepared regarding the TiO2 NP‐based photothermal and photodynamic therapies to overcome the obstacles of traditional TiO2 NPs and, therefore, broaden the use of these nanostructures for further biomedical purposes.
The large surface area/volume ratio and controllable surface conformation of electrospun nanofibers (ENFs) make them highly attractive in applications where a large surface area is desired, such as sensors and affinity membranes. In this study, nanocomposite-based ENFs were produced and immobilization of Anti-CRP was carried out for the non-invasive detection of C-reactive protein (CRP). Initially, the synthesis of graphene oxide (GO) was carried out and it was modified with magnetic nanoparticles (MNP, Fe3O4) and polydopamine (PDA). Catechol-containing and quinone-containing functional groups were created on the nanocomposite surface for the immobilization of Anti-CRP. Polystyrene (PS) solution was mixed with rGO-MNP-PDA nanocomposite and PS/rGO-MNP-PDA ENFs were produced with bead-free, smooth, and uniform. The surface of the screen-printed carbon electrode (SPCE) was covered with PS/rGO-MNP-PDA ENFs by using the electrospinning technique under the determined optimum conditions. Next, Anti-CRP immobilization was carried out and the biofunctional surface was created on the PS/rGO-MNP-PDA ENFs coated SPCE. Moreover, PS/rGO-PDA/Anti-CRP and PS/MNP-PDA/Anti-CRP immunosensors were also prepared and the effect of each component in the nanocomposite-based electrospun nanofiber (MNP, rGO) on the sensor response was investigated. The analytic performance of the developed PS/rGO-MNP-PDA/Anti-CRP, PS/rGO-PDA/Anti-CRP, and PS/MNP-PDA/Anti-CRP immunosensors were examined by performing electrochemical measurements in the presence of CRP. The linear detection range of PS/rGO-MNP-PDA/Anti-CRP immunosensor was found to be from 0.5 to 60 ng/mL and the limit of detection (LOD) was calculated as 0.33 ng/mL for CRP. The PS/rGO-MNP-PDA/Anti-CRP immunosensor also exhibited good repeatability with a low coefficient of variation.
In this study, poly-Ɛ-caprolactone (PCL) and poly(acrylic) acid (PAA)-based electrospun nanofibers were prepared for the immobilization of pyranose oxidase (PyOx) to design a bioelectrochemical detection system. Different amounts of PAA were used to increase hydrophilicity (decreased contact angle) of the PCL electrospun nanofibers. To provide a multipoint attachment side to bind PyOx by covalent bonds, various amounts of high generation (G5) poly(amidoamine) (PAMAM) dendrimer with amino groups were added to the PCL:PAA backbone. To attach PyOx onto the PCL:PAA/PAMAM electrospun nanofibers, glutaraldehyde was used as a homobifunctional crosslinker. Firstly, PCL:PAA ratio was optimized to obtain the best electrospun nanofibers without beads and with decreased contact angle. Then, the effect of the PAMAM amount on the morphology of PCL:PAA and contact angle was tested. The obtained PCL:PAA/PAMAM electrospun nanofiber was characterized by scanning electron microscopy (SEM). Then, the presence of PAMAM in the structure and the success of PyOx immobilization onto PCL:PAA/PAMAM were proven by SEM and an energy dispersive X-ray analyzer (SEM-EDX). Finally, PCL:PAA/PAMAM/PyOx was characterized, calibrated, and applied to analyze glucose in samples without any interfering effect of some chemicals. Briefly, the nanofibers modification with dendrimers and the conjugation of PyOx onto formed nanostructures was successfully performed, and a novel electrospun nanofiber-based sensor system was developed for target detection.
Over various scientific fields in biochemistry, amino acids have been highlighted in research works. Protein, peptide- and amino acid-based drug delivery systems have proficiently transformed nanotechnology via immense flexibility in their features for attaching various drug molecules and biodegradable polymers. In this regard, novel nanostructures including carbon nanotubes, electrospun carbon nanofibers, gold nanoislands, and metal-based nanoparticles have been introduced as nanosensors for accurate detection of these organic compounds. These nanostructures can bind the biological receptor to the sensor surface and increase the surface area of the working electrode, significantly enhancing the biosensor performance. Interestingly, protein-based nanocarriers have also emerged as useful drug and gene delivery platforms. This is important since, despite recent advancements, there are still biological barriers and other obstacles limiting gene and drug delivery efficacy. Currently available strategies for gene therapy are not cost-effective, and they do not deliver the genetic cargo effectively to target sites. With rapid advancements in nanotechnology, novel gene delivery systems are introduced as nonviral vectors such as protein, peptide, and amino acid-based nanostructures. These nano-based delivery platforms can be tailored into functional transformation using proteins and peptides ligands based nanocarriers, usually overexpressed in the specified diseases. The purpose of this review is to shed light on traditional and nanotechnology-based methods to detect amino acids, peptides, and proteins. Furthermore, new insights into the potential of amino protein-based nanoassemblies for targeted drug delivery or gene transfer are presented.