Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also known as 2019-nCov or nCovid-19) outbreak has become a huge public health issue due to its rapid transmission making it a global pandemic. Currently, there are no vaccines or drugs available for nCovid-19, hence early detection is crucial to help and manage the outbreak. Here, we report an inhouse built biosensor device (eCovSens) and compare it with a commercial potentiostat machine for the detection of nCovid-19 spike protein antigen (nCovid-19 Ag) in spiked saliva samples. A potentiostat based sensor was fabricated using fluorine doped tin oxide electrode (FTO) drop casted with gold nanoparticle (AuNPs) and immobilized with nCovid-19 monoclonal antibody (nCovid-19 Ab) to measure change in the electrical conductivity. Similarly, eCovSens was used to measure change in electrical conductivity by immobilizing nCovid-19 Ab on screen printed carbon electrode (SPCE). The performances of both sensors were recorded upon interaction of nCovid-19 Ab with its specific nCovid-19 Ag. Under optimum conditions, the FTO based immunosensor and proposed SPCE-based biosensor device displayed high sensitivity for early detection of nCovid-19 Ag, ranging from 1 fM to 1 µM. Our in-house developed eCovSens device can successfully detect nCovid-19 Ag at 10 fM concentration in standard buffer that is in close agreement with FTO/AuNPs sensor where AuNPs were used for the amplification of the electrical signal. The limit of detection (LOD) was found to be 90 fM with eCovSens and 120 fM with potentiostst in case of spiked saliva samples. The proposed portable point of care (PoC) eCovSens device can be used as an alternative diagnostic tool for the rapid (within 10-30 s) detection of nCovid-19 Ag traces directly in patient saliva samples that displayed high sensitivity, stability, and specificity.
Following the identification of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, we are now again facing a global highly pathogenic novel coronavirus (SARS-CoV-2) epidemic. Although the lungs are one of the most critically affected organs, several other organs, including the brain may also get infected. Here, we have highlighted that SARS-CoV-2 might infect the central nervous system (CNS) through the olfactory bulb. From the olfactory bulb, SARS-CoV-2 may target the deeper parts of the brain including the thalamus and brainstem by trans-synaptic transfer described for many other viral diseases. Following this, the virus might infect the respiratory center of brain, which could be accountable for the respiratory breakdown of COVID-19 patients. Therefore, it is important to screen the COVID-19 patients for neurological symptoms as well as possibility of the collapse of the respiratory center in the brainstem should be investigated in depth.
Delivery of imaging reagents and drugs to tumors is essential for cancer diagnosis and therapy. In addition to therapeutic and diagnostic functionalities, peptides have potential benefits such as biocompatibility, ease to synthesize, smaller size, by-passing off-target side effects, and achieving the beneficial effects with lower-administered dosages. A particular type of peptide known as cell penetrating peptides (CPP) have been predominantly studied during last twenty years as they are not only capable to translocate themselves across membranes but also allow carrier drugs to translocate across plasma membrane, by different mechanisms depending on the CPP. This is of great potential importance in drug delivery systems, as the ability to pass across membranes is crucial to many drug delivery systems. In spite of significant progress in design and application of CPP, more investigations are required to further improve their delivery to tumors, with reduced side-effect and enhanced therapeutic efficacy. In this review, we emphasis on current advancements in preclinical and clinical trials based on using CPP for more efficient delivery of anti-cancer drugs and imaging reagents to cancer tissues and individual cells associated with them. We discuss the evolution of the CPPs-based strategies for targeted delivery, their current status and strengths, along with summarizing the role of CPPs in targeted drug delivery. We also discuss some recently reported diagnostic applications of engineered protease-responsive substrates and activable imaging complexes. We highlight the recent clinical trial data by providing a road map for better design of the CPPs for future preclinical and clinical applications.
Magnetic Particle Imaging (MPI) is a new real-time imaging modality, which promises high tracer mass sensitivity and spatial resolution directly generated from iron oxide nanoparticles. In this study, monodisperse iron oxide nanoparticles with median core diameters ranging from 14 to 26 nm were synthesized and their surface was conjugated with lactoferrin to convert them into brain glioma targeting agents. The conjugation was confirmed with the increase of the hydrodynamic diameters, change of zeta potential, and Bradford assay. Magnetic particle spectrometry (MPS), performed to evaluate the MPI performance of these nanoparticles, showed no change in signal after lactoferrin conjugation to nanoparticles for all core diameters, suggesting that the MPI signal is dominated by Néel relaxation and thus independent of hydrodynamic size difference or presence of coating molecules before and after conjugations. For this range of core sizes (14-26 nm), both MPS signal intensity and spatial resolution improved with increasing core diameter of nanoparticles. The lactoferrin conjugated iron oxide nanoparticles (Lf-IONPs) showed specific cellular internalization into C6 cells with a 5-fold increase in MPS signal compared to IONPs without lactoferrin, both after 24h incubation. These results suggest that Lf-IONPs can be used as tracers for targeted brain glioma imaging using MPI.
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