DNA Aptamer Integrated Hydrogel Nanocomposites on Screen Printed Gold Electrodes for Point-of-Care Detection of Testosterone in Human Serum.

This work describes the development and evaluation of a novel electrochemical aptasensor for testosterone detection. The sensor utilizes a specifically designed DNA immobilized on a screen-printed gold electrode (SPGE) modified with a conductive hydrogel and gold nanoparticles (HG/NP) composite. The aptasensor exhibited a dose-dependent response to testosterone (0.05 to 50 ng/mL) with a detection limit of 0.14 ng/mL and a good sensitivity of 0.23 µA ng-1 mL cm-2. The sensor displayed excellent selectivity towards testosterone compared to structurally similar steroid hormones. Importantly, the incorporation of HG/NP not only improved the sensor's conductivity but also acted as an antifouling layer, minimizing signal interference from non-specific biomolecule interactions in complex biological samples like human serum. The results obtained from the aptasensor showed good correlation with a standard ELISA method, demonstrating its effectiveness in real-world scenarios.

Diagnostic potential of exosomal extracellular vesicles in oncology.

Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implicationsEVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment.

Multi-functional auto-fluorescent nanogels for theranostics.

Here in the present article, the state of art for nanotechnology-enabled nanogel theranostics and the upcoming concepts in nanogel-based therapeutics are summarized. The benefits, innovation, and prospects of nanogel technology are also briefly presented.

Machine learning assisted-nanomedicine using magnetic nanoparticles for central nervous system diseases.

Magnetic nanoparticles possess unique properties distinct from other types of nanoparticles developed for biomedical applications. Their unique magnetic properties and multifunctionalities are especially beneficial for central nervous system (CNS) disease therapy and diagnostics, as well as targeted and personalized applications using image-guided therapy and theranostics. This review discusses the recent development of magnetic nanoparticles for CNS applications, including Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, and drug addiction. Machine learning (ML) methods are increasingly applied towards the processing, optimization and development of nanomaterials. By using data-driven approach, ML has the potential to bridge the gap between basic research and clinical research. We review ML approaches used within the various stages of nanomedicine development, from nanoparticle synthesis and characterization to performance prediction and disease diagnosis.

Emerging trends in point-of-care biosensing strategies for molecular architectures and antibodies of SARS-CoV-2.

COVID-19, a highly contagious viral infection caused by the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV-2), has turned out to be a viral pandemic then ravaged many countries worldwide. In the recent years, point-of-care (POC) biosensors combined with state-of-the-art bioreceptors, and transducing systems enabled the development of novel diagnostic tools for rapid and reliable detection of biomarkers associated with SARS-CoV-2. The present review thoroughly summarises and discusses various biosensing strategies developed for probing SARS-CoV-2 molecular architectures (viral genome, S Protein, M protein, E protein, N protein and non-structural proteins) and antibodies as a potential diagnostic tool for COVID-19. This review discusses the various structural components of SARS-CoV-2, their binding regions and the bioreceptors used for recognizing the structural components. The various types of clinical specimens investigated for rapid and POC detection of SARS-CoV-2 is also highlighted. The importance of nanotechnology and artificial intelligence (AI) approaches in improving the biosensor performance for real-time and reagent-free monitoring the biomarkers of SARS-CoV-2 is also summarized. This review also encompasses existing practical challenges and prospects for developing new POC biosensors for clinical monitoring of COVID-19.

Anti-inflammatory effects of CBD in human microglial cell line infected with HIV-1.

Human immunodeficiency virus (HIV) infection is associated with a chronic inflammatory stage and continuous activation of inflammasome pathway. We studied the anti-inflammatory effects of the compound cannabidiol (CBD) in comparison with Δ (9)-tetrahydrocannabinol [Δ(9)-THC] in human microglial cells (HC69.5) infected with HIV. Our results showed that CBD reduced the production of various inflammatory cytokines and chemokines such as MIF, SERPIN E1, IL-6, IL-8, GM-CSF, MCP-1, CXCL1, CXCL10, and IL-1 ß compared to Δ(9)-THC treatment. In addition, CBD led to the deactivation of caspase 1, reduced NLRP3 gene expression which play a crucial role in the inflammasome cascade. Furthermore, CBD significantly reduced the expression of HIV. Our study demonstrated that CBD has anti-inflammatory properties and exhibits significant therapeutic potential against HIV-1 infections and neuroinflammation.

Drug Delivery to the Brain: Recent Advances and Unmet Challenges.

Brain cancers and neurodegenerative diseases are on the rise, treatments for central nervous system (CNS) diseases remain limited. Despite the significant advancement in drug development technology with emerging biopharmaceuticals like gene therapy or recombinant protein, the clinical translational rate of such biopharmaceuticals to treat CNS disease is extremely poor. The blood-brain barrier (BBB), which separates the brain from blood and protects the CNS microenvironment to maintain essential neuronal functions, poses the greatest challenge for CNS drug delivery. Many strategies have been developed over the years which include local disruption of BBB via physical and chemical methods, and drug transport across BBB via transcytosis by targeting some endogenous proteins expressed on brain-capillary. Drug delivery to brain is an ever-evolving topic, although there were multiple review articles in literature, an update is warranted due to continued growth and new innovations of research on this topic. Thus, this review is an attempt to highlight the recent strategies employed to overcome challenges of CNS drug delivery while emphasizing the necessity of investing more efforts in CNS drug delivery technologies parallel to drug development.

Recent Advances in Nanotherapeutics for Neurological Disorders.

Neurological disorders remain a significant health and economic burden worldwide. Addressing the challenges imposed by existing drugs, associated side- effects, and immune responses in neurodegenerative diseases is essential for developing better therapies. The immune activation in a diseased state has complex treatment protocols and results in hurdles for clinical translation. There is an immense need for the development of multifunctional nanotherapeutics with various properties to address the different limitations and immune interactions exhibited by the existing therapeutics. Nanotechnology has proven its potential to improve therapeutic delivery and enhance efficacy. Promising advancements have been made in developing nanotherapies that can be combined with CRISPR/Cas9 or siRNA for a targeted approach with unique potential for clinical translation. Engineering natural exosomes derived from mesenchymal stem cells (MSCs), dendritic cells (DCs), or macrophages to both deliver therapeutics and modulate the immune responses to tumors or in neurodegenerative disease (ND) can allow for targeted personalized therapeutic approaches. In the present review, we summarize and overview the recent advances in nanotherapeutics in addressing the existing treatment limitations and neuroimmune interactions for developing ND therapies and provide insights into the upcoming advancements in nanotechnology-based nanocarriers.

Cannabidiol for neurodegenerative disorders: A comprehensive review.

Despite the significant advances in neurology, the cure for neurodegenerative conditions remains a formidable task to date. Among various factors arising from the complex etiology of neurodegenerative diseases, neuroinflammation and oxidative stress play a major role in pathogenesis. To this end, some phytocannabinoids isolated from Cannabis sativa (widely known as marijuana) have attracted significant attention as potential neurotherapeutics. The profound effect of ∆9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, has led to the discovery of the endocannabinoid system as a molecular target in the central nervous system (CNS). Cannabidiol (CBD), the major non-psychoactive component of cannabis, has recently emerged as a potential prototype for neuroprotective drug development due to its antioxidant and anti-inflammatory properties and its well-tolerated pharmacological behavior. This review briefly discusses the role of inflammation and oxidative stress in neurodegeneration and demonstrates the neuroprotective effect of cannabidiol, highlighting its general mechanism of action and disease-specific pathways in Parkinson's disease (PD) and Alzheimer's disease (AD). Furthermore, we have summarized the preclinical and clinical findings on the therapeutic promise of CBD in PD and AD, shed light on the importance of determining its therapeutic window, and provide insights into identifying promising new research directions.

Recent advances, status, and opportunities of magneto-electric nanocarriers for biomedical applications.

Magneto-electric (ME) materials with core-shell architecture where the core is made of magnetic materials have emerged as an attractive nanomaterial due to the coupling of magnetic and electric properties in the same material and the fact that both fields can be controlled which allows an on-demand, transport and release of loaded cargo. Over the last decade, biomedical engineers and researchers from various interdisciplinary fields have successfully demonstrated promising properties ranging from therapeutic delivery to sensing, and neuromodulation using ME materials. In this review, we systematically summarize developments in various biomedical fields using the nanoforms of these materials. Herein, we also highlight various promising biomedical applications where the ME nanocarriers are encapsulated in other materials such as gels and liposomes and their potential for promising therapeutics and diagnostic applications.

Gold nanocubes embedded biocompatible hybrid hydrogels for electrochemical detection of H2O2.

Smart electrochemical biosensors have emerged as a promising alternative analytical diagnostic tool in recent clinical practice. However, improvement in the biocompatibility and electrical conductivity of the biosensor matrix and the immobilization of various bioactive molecules such as enzymes still remain challenging. The present research reports the synthesis of a biocompatible hydrogel network and its integration with gold nanocubes (AuNCs) for developing a novel biosensor with improved functionality. The interpenetrating hydrogel network consist of biopolymers developed using graft co-polymerization of ß-cyclodextrin (ß-CD) and chitosan (CS). The novelty of this work is in integrating the CS-g-ß-CD hydrogel network with conductive AuNCs for improving hydrogel conductivity, biosensor sensitivity and use of the material for a biocompatible sensor. The present protocol advances the state of the art for the utilization of biopolymeric hydrogels system in synergy with an enzymatic biosensing protocol for exclusively detecting hydrogen peroxide (H2O2). Immobilization of the mitochondrial protein, cytochrome c (cyt c) into the hydrogel nanocomposite matrix was performed via thiol cross-linking. This organic-inorganic hybrid nanocomposite hydrogel matrix exhibited high biocompatibility (RAW 264.7 and N2a cell lines), improved electrical conductivity to attain high sensitivity (1.2 mA mM-1 cm-2) and a low detection limit (15 × 10-9 M) for H2O2.

Development of Multifunctional Biopolymeric Auto-Fluorescent Micro- and Nanogels as a Platform for Biomedical Applications.

The emerging field of theranostics for advanced healthcare has raised the demand for effective and safe delivery systems consisting of therapeutics and diagnostics agents in a single monarchy. This requires the development of multi-functional bio-polymeric systems for efficient image-guided therapeutics. This study reports the development of size-controlled (micro-to-nano) auto-fluorescent biopolymeric hydrogel particles of chitosan and hydroxyethyl cellulose (HEC) synthesized using water-in-oil emulsion polymerization technique. Sustainable resource linseed oil-based polyol is introduced as an element of hydrophobicity with an aim to facilitate their ability to traverse the blood-brain barrier (BBB). These nanogels are demonstrated to have salient features such as biocompatibility, stability, high cellular uptake by a variety of host cells, and ability to transmigrate across an in vitro BBB model. Interestingly, these unique nanogel particles exhibited auto-fluorescence at a wide range of wavelengths 450-780 nm on excitation at 405 nm whereas excitation at 710 nm gives emission at 810 nm. In conclusion, this study proposes the developed bio-polymeric fluorescent micro- and nano- gels as a potential theranostic tool for central nervous system (CNS) drug delivery and image-guided therapy.

Impact of Nanoclay on the pH-Responsiveness and Biodegradable Behavior of Biopolymer-Based Nanocomposite Hydrogels.

This research work deployed free radical polymerization for the development of pH-responsive hybrid nanocomposite hydrogels (NCHs) with the formation of improved interpenetrating networks (IPN). The crosslinked biopolymeric system was composed of (chitosan (CH)/guar gum (GG)/polyol) and a nanofiller (Cloisite 30B). The study was aimed to investigate the role of Cloisite 30B as a nanofiller and linseed oil-derived polyol to induce stable interpenetrating networks in chitosan‒guar gum-based hydrogels. FT-IR analysis confirmed the formation of crosslinked networks with the formation of hydrogen bonds in the synthesized NCHs. Thermogravimetric analysis and differential scanning calorimetry revealed high thermal stability of the NCHs. The hydrolytic and soil burial degradation tests confirmed the biodegradability of the synthesized NCHs. An extraordinarily high swelling capacity in a buffer solution of pH 4.0 and 7.4 demonstrated their pH-responsive behavior. It has been demonstrated that even the minimal addition of polyol to the guar gum-based hydrogels has influenced the stability and characteristic features such as high swelling capacity owing to the formation of interpenetrating networks and the biodegradability of the hydrogels.

Na-Montmorillonite-Dispersed Sustainable Polymer Nanocomposite Hydrogel Films for Anticancer Drug Delivery.

Nanocomposite hydrogels have found a wide scope in regenerative medicine, tissue engineering, and smart drug delivery applications. The present study reports the formulations of biocompatible nanocomposite hydrogel films using carboxymethyl cellulose-hydroxyethyl cellulose-acrylonitrile-linseed oil polyol (CHAP) plain hydrogel and Na-montmorillonite (NaMMT) dispersed CHAP nanocomposite hydrogel films (NaCHAP) using solution blending technique. The structural, morphological, and mechanical properties of resultant nanocomposite hydrogel films were further investigated to analyze the effects of polyol and NaMMT on the characteristic properties. The synergistic effect of polyol and nanofillers on the mechanical strength and sustained drug-release behavior of the resultant hydrogel films was studied, which revealed that the increased cross-link density of hydrogels enhanced the elastic modulus (up to 99%) and improved the drug retention time (up to 72 h at both pHs 7.4 and 4.0). The release rate of cisplatin in nanocomposite hydrogel films was found to be higher in CHAP-1 (83 and 69%) and CHAP-3 (79 and 64%) than NaCHAP-3 (77 and 57%) and NaCHAP-4 (73 and 54%) at both pHs 4.0 and 7.4, respectively. These data confirmed that the release rate of cisplatin in nanocomposite hydrogel films was pH-responsive and increased with decrease of pH. All nanocomposite hydrogel films have exhibited excellent pH sensitivity under buffer solution of various pHs (1.0, 4.0, 7.4, and 9.0). The in vitro biocompatibility and cytotoxicity tests of these films were also conducted using 3-(4,5-dimethylthiazole-2-yl-2,5-diphenyl tetrazolium bromide) assay of human embryonic kidney (HEK-293) and human breast cancer (MCF-7) cell lines up to 48 h, which shows their biocompatible nature. However, cisplatin-loaded nanocomposite hydrogel films effectively inhibited the growth of human breast MCF-7 cancer cells. These studies suggested that the proposed nanocomposite hydrogel films have shown promising application in therapeutics, especially for anticancer-targeted drug delivery.

pH-Responsive Biocompatible Nanocomposite Hydrogels for Therapeutic Drug Delivery.

The present study reports the formulations of biocompatible nanocomposite hydrogels using chitosan (CH), poly(vinyl alcohol) (PVA), oleo polyol, and fumed silica (SiO2) via a free radical polymerization method for anti-cancer drug delivery. Structural, morphological, and mechanical analyses were conducted using FT-IR spectroscopy, scanning electron microscopy, transmission electron microscopy, and rheological techniques. The effect of SiO2 concentration on mechanical strength, swelling ratios, morphological, and drug delivery behavior was investigated. The incorporation of SiO2 nanoparticles in hydrogels resulted in a significant enhancement in its properties. MTT assay of human embryonic kidney (HEK-293) and human colon (HCT116) cancer cell lines was conducted for up to 48 h to evaluate biocompatibility and cytotoxicity. These studies confirmed the biocompatible nature of nanocomposite hydrogels. Cisplatin-loaded nanocomposite hydrogels exhibit sustained release as compared to free cisplatin at pH 4.0 and pH 7.4. The in vitro cytotoxicity test of cisplatin-loaded hydrogels using the HCT116 cancer cell line indicates that these hydrogels successfully inhibit the growth of HCT116 cancer cells. The results of in vitro tests for drug loading, sustained release, biodegradability, biocompatibility, and anti-proliferative activity of cisplatin-loaded nanocomposite hydrogels suggest that, in the future, they may find applications in the development of topical (in vivo, in the form of tablets) drug delivery systems.

Biocompatible and mechanically robust nanocomposite hydrogels for potential applications in tissue engineering.

The synergistic contributions of nanofillers and polymer matrix induce remarkable properties in nanocomposite hydrogels. Present article reports the facile synthesis of biocompatible nanocomposite hydrogels using microporous multi wall carbon nanotubes (MWCNTs) dispersed chitosan (CH)-Acrylonitrile (AN), N,N'-methylenebisacrylamide (MBAAm) and linseed polyol through solution blending method. Polyol and N,N'-methylenebisacrylamide (MBAAm) was used as the crosslinking agent. The structural characterization and formation of highly crosslinked network with dendrimer morphology was confirmed by FT-IR and scanning electron microscope (SEM) analysis. In addition, transmission electron microscope (TEM) was employed to visualize the size and proper dispersion of MWCNT in the polymer matrices. The strong mechanical strength exhibited by these hydrogel films was confirmed by the tensile strength analysis. The dispersion of the conductive nanofillers, like MWCNTs has significantly enhanced the strength, which revealed unique characteristics of these hydrogel films. The high swelling capacity and sustained expansion of hydrogel films were confirmed in the buffer solutions of pH4 and 7.4. The biodegradability of these films was estimated by hydrolytic and soil burial tests. The biocompatibility test was conducted on Human Embryonic Kidney (HEK-293) cell line, which confirmed the non-toxic and biocompatible nature of these films. Incorporation of carbon nanotubes (MWCNTs) in the polymer matrix enhanced the film forming properties, high modulus and tensile strength, swelling ability, biodegradable and biocompatibility. These properties can be finely tuned through the variation of MWCNT concentrations, as a result these nanostructure hydrogel films have potential scope for their diverse applications in the field of tissue engineering.

Advances in Carbon Nanotubes-Hydrogel Hybrids in Nanomedicine for Therapeutics.

In spite of significant advancement in hydrogel technology, low mechanical strength and lack of electrical conductivity have limited their next-level biomedical applications for skeletal muscles, cardiac and neural cells. Host-guest chemistry based hybrid nanocomposites systems have gained attention as they completely overcome these pitfalls and generate bioscaffolds with tunable electrical and mechanical characteristics. In recent years, carbon nanotube (CNT)-based hybrid hydrogels have emerged as innovative candidates with diverse applications in regenerative medicines, tissue engineering, drug delivery devices, implantable devices, biosensing, and biorobotics. This article is an attempt to recapitulate the advancement in synthesis and characterization of hybrid hydrogels and provide deep insights toward their functioning and success as biomedical devices. The improved comparative performance and biocompatibility of CNT-hydrogels hybrids systems developed for targeted biomedical applications are addressed here. Recent updates toward diverse applications and limitations of CNT hybrid hydrogels is the strength of the review. This will provide a holistic approach toward understanding of CNT-based hydrogels and their applications in nanotheranostics.

Nanogels as potential drug nanocarriers for CNS drug delivery.

Hydrogel-based drug delivery systems (DDSs) have versatile applications such, as tissue engineering, scaffolds, drug delivery, and regenerative medicines. The drawback of higher size and poor stability in such DDSs are being addressed by developing nano-sized hydrogel particles, known as nanogels, to achieve the desired biocompatibility and encapsulation efficiency for better efficacy than conventional bulk hydrogels. In this review, we describe advances in the development of nanogels and their promotion as nanocarriers to deliver therapeutic agents to the central nervous system (CNS). We also discuss the challenges, possible solutions, and future prospects for the use of nanogel-based DDSs for CNS therapies.

A sensitive electrochemical immunosensor for label-free detection of Zika-virus protein.

This work, as a proof of principle, presents a sensitive and selective electrochemical immunosensor for Zika-virus (ZIKV)-protein detection using a functionalized interdigitated micro-electrode of gold (IDE-Au) array. A miniaturized IDE-Au immunosensing chip was prepared via immobilization of ZIKV specific envelop protein antibody (Zev-Abs) onto dithiobis(succinimidyl propionate) i.e., (DTSP) functionalized IDE-Au (electrode gap/width of 10 µm). Electrochemical impedance spectroscopy (EIS) was performed to measure the electrical response of developed sensing chip as a function of ZIKV-protein concentrations. The results of EIS studies confirmed that sensing chip detected ZIKV-protein selectively and exhibited a detection range from 10 pM to 1 nM and a detection limit of 10 pM along with a high sensitivity of 12 kΩM-1. Such developed ZIKV immune-sensing chip can be integrated with a miniaturized potentiostat (MP)-interfaced with a smartphone for rapid ZIKV-infection detection required for early stage diagnostics at point-of-care application.

Nanocomposite Hydrogels: Advances in Nanofillers Used for Nanomedicine.

The ongoing progress in the development of hydrogel technology has led to the emergence of materials with unique features and applications in medicine. The innovations behind the invention of nanocomposite hydrogels include new approaches towards synthesizing and modifying the hydrogels using diverse nanofillers synergistically with conventional polymeric hydrogel matrices. The present review focuses on the unique features of various important nanofillers used to develop nanocomposite hydrogels and the ongoing development of newly hydrogel systems designed using these nanofillers. This article gives an insight in the advancement of nanocomposite hydrogels for nanomedicine.