Outlook of various diagnostics and nanodiagnostic techniques for COVID-19.

The sudden outbreak of the coronavirus disease 2019 (COVID-19) pandemic has brought to the fore the existing threat of disease-causing pathogens that affect public health all over the world. It has left the best healthcare systems struggling to contain the spread of disease and its consequences. Under challenging circumstances, several innovative technologies have emerged that facilitated quicker diagnosis and treatment. Nanodiagnostic devices are biosensing platforms developed using nanomaterials such as nanoparticles, nanotubes, nanowires, etc. These devices have the edge over conventional techniques such as reverse transcription-polymerase chain reaction (RT-PCR) because of their ease of use, quicker analysis, possible miniaturization, and scope for use in point-of-care (POC) treatment. This review discusses the techniques currently used for COVID-19 diagnosis, emphasizing nanotechnology-based diagnostic devices. The commercialized nanodiagnostic devices in various research and development stages are also reviewed. The advantages of nanodiagnostic devices over other techniques are discussed, along with their limitations. Additionally, the important implications of the utility of nanodiagnostic devices in COVID-19, their prospects for future development for use in clinical and POC settings, and personalized healthcare are also discussed.

Recent advances in point-of-care diagnostics for oral cancer.

Early-stage diagnosis is a crucial step in reducing the mortality rate in oral cancer cases. Point-of-care (POC) devices for oral cancer diagnosis hold great future potential in improving the survival rates as well as the quality of life of oral cancer patients. The conventional oral examination followed by needle biopsy and histopathological analysis have limited diagnostic accuracy. Besides, it involves patient discomfort and is not feasible in resource-limited settings. POC detection of biomarkers and diagnostic adjuncts has emerged as non- or minimally invasive tools for the diagnosis of oral cancer at an early stage. Various biosensors have been developed for the rapid detection of oral cancer biomarkers at the point-of-care. Several optical imaging methods have also been employed as adjuncts to detect alterations in oral tissue indicative of malignancy. This review summarizes the different POC platforms developed for the detection of oral cancer biomarkers, along with various POC imaging and cytological adjuncts that aid in oral cancer diagnosis, especially in low resource settings. Various immunosensors and nucleic acid biosensors developed to detect oral cancer biomarkers are summarized with examples. The different imaging methods used to detect oral tissue malignancy are also discussed herein. Additionally, the currently available commercial devices used as adjuncts in the POC detection of oral cancer are emphasized along with their characteristics. Finally, we discuss the limitations and challenges that persist in translating the developed POC techniques in the clinical settings for oral cancer diagnosis, along with future perspectives.

Perspectives of characterization and bioconjugation of gold nanoparticles and their application in lateral flow immunosensing.

Gold nanoparticles (AuNPs) are an important component in the field of biomedical diagnostics. Because of its unique physicochemical properties, AuNPs have been widely used in biomedical applications such as photothermal cancer therapy, drug delivery, optical imaging, labeling, and biosensing. In this review, we have described synthesis and characterization techniques for AuNPs with recent advancements. Characterization of AuNPs has played an important role in directing its application in various fields and elaborated understanding of its functioning. The characterization techniques used for the analysis of AuNPs utilize its intrinsic properties, such as surface plasmon resonance (SPR) and size-dependent shift in absorption. These properties of AuNPs are furthermore used for the characterization of bioconjugated AuNPs. Surface conjugation of the AuNPs with biomolecules is explored widely for its use in numerous biosensing applications. Biosensor-based diagnostic devices use AuNPs conjugated with a sensing probe for the detection of a specific analyte. AuNPs are also commonly used as a colorimetric sensor in various point-of-care diagnostic techniques. Lateral flow immunosensing (LFIS) technique utilizes AuNPs for the rapid and sensitive detection of various analytes. LFIS is a paper-based detection technique, where the sample containing the analyte flows through the membrane, interacts with immobilized counterparts, and produces results using a detection probe. AuNPs are used as color markers in LFIS, and the presence of an analyte is indicated by the appearance of colored lines on the membrane. The color is a result of the accumulation of AuNP complexes containing the analyte and probe. Effect of characterization parameters of AuNPs on the sensitivity of LFIS, advantages, and disadvantages of using AuNPs for LFIS are discussed concerning the recent reports. Recent applications of AuNPs in LFIS development for the detection of various biomarkers are summarized comprehensively in the table. The review may offer significant insight into the utility of AuNPs for application in the LFIS technique for future development. Graphical abstract Schematic representation of the various applications of gold nanoparticles.

Arginolipid: A membrane-active antifungal agent and its synergistic potential to combat drug resistance in clinical Candida isolates.

Antifungal drug resistance exhibits a major clinical challenge for treating nosocomial fungal infections. To find a possible solution, we synthesized and studied the antifungal activities of three different arginolipids (Nα -acyl-arginine ethyl ester) against clinical drug-resistant isolates of Candida. The most active arginolipid, oleoyl arginine ethyl ester (OAEE) consisting of a long unsaturated hydrophobic chain, was tested for its mode of action, which revealed that it altered ergosterol biosynthesis and compromised the fungal cell membrane. Also, OAEE was found to exhibit synergistic interactions with fluconazole (FLU) or amphotericin B (AmB) against planktonic Candida cells, wherein it reduced the inhibitory concentrations of these drugs to their in vitro susceptible range. Studies conducted against the C. tropicalis biofilm revealed that the OAEE+AmB combination synergistically reduced the metabolic activity and hyphal density in biofilms, whereas OAEE+FLU was found to be additive against most cases. Finally, the evaluated selective toxicity of OAEE toward fungal cells over mammalian cells could establish it as an alternative treatment for combating drug-resistant Candida infections.

Current status of point-of-care diagnostic devices in the Indian healthcare system with an update on COVID-19 pandemic.

Point-of-care (POC) diagnostic device is an instrument that is used to acquire particular clinical information of patients in clinical as well as resource-limited settings. The conventional clinical diagnostic procedure requires high-end and costly instruments, an expert technician for operation and result interpretation, longer time, etc. that ultimately makes it exhausting and expensive. Although there are a lot of improvements in the medical facilities in the Indian healthcare system, the use of POC diagnostic devices is still in its nascent phase. This review illustrates the status of POC diagnostic devices currently used in clinical setups along with constraints in their use. The devices and technologies that are in the research and development phase across the country that has tremendous potential to elevate the clinical diagnostics scenario along with the diagnosis of ongoing COVID-19 pandemic are emphasized. The implications of using POC diagnostic devices and the future objectives for technological advancements that may eventually uplift the status of healthcare and related sectors in India are also discussed here.

Oral cancer diagnosis and perspectives in India.

Globally, oral cancer is the sixth most common type of cancer with India contributing to almost one-third of the total burden and the second country having the highest number of oral cancer cases. Oral squamous cell carcinoma (OSCC) dominates all the oral cancer cases with potentially malignant disorders, which is also recognized as a detectable pre-clinical phase of oral cancer. Tobacco consumption including smokeless tobacco, betel-quid chewing, excessive alcohol consumption, unhygienic oral condition, and sustained viral infections that include the human papillomavirus are some of the risk aspects for the incidence of oral cancer. Lack of knowledge, variations in exposure to the environment, and behavioral risk factors indicate a wide variation in the global incidence and increases the mortality rate. This review describes various risk factors related to the occurrence of oral cancer, the statistics of the distribution of oral cancer in India by various virtues, and the socio-economic positions. The various conventional diagnostic techniques used routinely for detection of the oral cancer are discussed along with advanced techniques. This review also focusses on the novel techniques developed by Indian researchers that have huge potential for application in oral cancer diagnosis.

In-vitro blood-brain barrier models for drug screening and permeation studies: an overview.

The blood-brain barrier (BBB) is comprised of brain microvascular endothelial central nervous system (CNS) cells, which communicate with other CNS cells (astrocytes, pericytes) and behave according to the state of the CNS, by responding against pathological environments and modulating disease progression. The BBB plays a crucial role in maintaining homeostasis in the CNS by maintaining restricted transport of toxic or harmful molecules, transport of nutrients, and removal of metabolites from the brain. Neurological disorders, such as NeuroHIV, cerebral stroke, brain tumors, and other neurodegenerative diseases increase the permeability of the BBB. While on the other hand, semipermeable nature of BBB restricts the movement of bigger molecules i.e. drugs or proteins (>500 kDa) across it, leading to minimal bioavailability of drugs in the CNS. This poses the most significant shortcoming in the development of therapeutics for CNS neurodegenerative disorders. Although the complexity of the BBB (dynamic and adaptable barrier) affects approaches of CNS drug delivery and promotes disease progression, understanding the composition and functions of BBB provides a platform for novel innovative approaches towards drug delivery to CNS. The methodical and scientific interests in the physiology and pathology of the BBB led to the development and the advancement of numerous in vitro models of the BBB. This review discusses the fundamentals of BBB structure, permeation mechanisms, an overview of all the different in-vitro BBB models with their advantages and disadvantages, and rationale of selecting penetration prediction methods towards the critical role in the development of the CNS therapeutics.

Graphene-based nanocomposites for sensitivity enhancement of surface plasmon resonance sensor for biological and chemical sensing: A review.

Surface plasmon resonance (SPR) offers exceptional advantages such as label-free, in-situ and real-time measurement ability that facilitates the study of molecular or chemical binding events. Besides, SPR lacks in the detection of various binding events, particularly involving low molecular weight molecules. This drawback ultimately resulted in the development of several sensitivity enhancement methodologies and their application in the various area. Among graphene materials, graphene-based nanocomposites stands out owing to its significant properties such as strong adsorption of molecules, signal amplification by optical, high carrier mobility, electronic bridging, ease of fabrication and therefore, have established as an important sensitivity enhancement substrate for SPR. Also, graphene-based nanocomposites could amplify the signal generated by plasmon material and increase the sensitivity of molecular detection up to femto to atto molar level. This review focuses on the current important developments made in the potential research avenue of SPR and fiber optics based SPR for chemical and biological sensing. Latest trends and challenges in engineering and applications of graphene-based nanocomposites enhanced sensors for detecting minute and low concentration biological and chemical analytes are reviewed comprehensively. This review may aid in futuristic designing approaches and application of grapheneous sensor platforms for sensitive plasmonic nano-sensors.

Fluorescence Stability of Mercaptopropionic Acid Capped Cadmium Telluride Quantum Dots in Various Biochemical Buffers.

Quantum dots are the semiconductor nanocrystals having unique optical and electronic properties. Quantum dots are category of fluorescent labels utilized for biological tagging, biosensing, bioassays, bioimaging and in vivo imaging as they exhibit very small size, signal brightness, photostability, tuning of light emission range, longer photoluminescence decay time as compared to organic dyes. In this work, we have synthesized and characterized mercaptopropionic acid capped cadmium telluride quantum dots (MPA-CdTe QDs) using hydrothermal method. The study further reports fluorescence intensity stability of quantum dots suspended in different buffers of varying concentration (1-100 mM), stored at various photophysical conditions. Fluorescence intensity values were reduced with increase in buffer concentration. When the samples were stored at room temperature in ambient light condition the quantum dots suspended in different buffers lost the fluorescence intensity after day 15 (except TRIS II). Fluorescence intensity values were found stable for more than 30 days when the samples were stored in dark condition. Samples stored in refrigerator displayed modest fluorescence intensity even after 300 days of storage. Thus, storage of MPA-CdTe QDs in refrigerator may be the suitable choice to maintain its fluorescence stability for longer time for further application.

Dual-purpose Injectable Doxorubicin Conjugated Alginate Gel Containing Polycaprolactone Microparticles for Anti-Cancer and Anti-Inflammatory Therapy.

BACKGROUND: In situ gel formulations have been widely reported as a carrier for sustained release delivery systems due to certain advantages such as targeted drug delivery, minimal invasiveness and potent therapeutic activity. OBJECTIVE: Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for anti-cancer and anti-inflammatory activity is reported. METHOD: Doxorubicin-conjugated alginate (dox-alg) gel was prepared using EDC-NHS chemistry and loaded with ibuprofen encapsulated polycaprolactone (PCL) microparticles (dox-alg composite). PCL microparticles were prepared by a solvent evaporation method (size 50 - 100µm). The gel was characterized using SEM, FTIR, XRD and TGA analysis. RESULTS: Dox-alg composite gel showed good syringeability and gel formation properties. Burst release was observed for both drugs within 24 h followed by sustained release till day 21. Doxorubicin released from composite showed considerable cytotoxic effect. Cell uptake was confirmed by confocal microscopy using MDA-MB-231 cells. Anti-inflammatory activity of ibuprofen released from composite gel was compared with the free drug. An injection of dox-alg composite gel in the tissue would fill the void created after tumor removal surgery, prevent the resuscitation of remnant cancerous cells and reduce inflammation. CONCLUSION: Thus, the dox-alg composite gel could be a potential agent for the dual anti-cancer and anti-inflammatory therapy.

Nanobiotechnology Perspectives on Prevention and Treatment of Ortho-paedic Implant Associated Infection.

Implants are an inevitable part of orthopaedic surgery. However, implant associated infection remains a major challenge for orthopaedic surgeons and researchers. This review focuses on current options available for prevention of implant associated infection, their drawbacks and future promising applications of nanotechnology-based approaches. Nanobiotechnology has shown remarkable progress in recent years especially in biomaterials, diagnostics, and drug delivery system. Although several applications of nanobiotechnology in orthopaedics have been described, few have elaborated their role in the prevention of implant related infection in orthopaedics. Novel "smart" drug delivery systems that release antibiotics locally in response to stimuli such as pH, temperature, enzymes or antigens; implant surface modification on a nanoscale to inhibit bacterial adhesion and propagation at the surgical site and biological approaches such as gene therapy to neutralize bacterial virulence and biomolecules to inhibit the quorum sensing adhesion of bacteria and disruption of biofilms can be used effectively to prevent orthopaedic implant related bacterial infection.