Chiral Induction in 2D Borophene Nanoplatelets through Stereoselective Boron-Sulfur Conjugation.

Chirality is a structural metric that connects biological and abiological forms of matter. Although much progress has been made in understanding the chemistry and physics of chiral inorganic nanoparticles over the past decade, almost nothing is known about chiral two-dimensional (2D) borophene nanoplatelets and their influence on complex biological networks. Borophene's polymorphic nature, derived from the bonding configurations among boron atoms, distinguishes it from other 2D materials and allows for further customization of its material properties. In this study, we describe a synthetic methodology for producing chiral 2D borophene nanoplatelets applicable to a variety of structural polymorphs. Using this methodology, we demonstrate feasibility of top-down synthesis of chiral χ3 and ß12 phases of borophene nanoplatelets via interaction with chiral amino acids. The chiral nanoplatelets were physicochemically characterized extensively by various techniques. Results indicated that the thiol presenting amino acids, i.e., cysteine, coordinates with borophene in a site-selective manner, depending on its handedness through boron-sulfur conjugation. The observation has been validated by circular dichroism, X-ray photoelectron spectroscopy, and 11B NMR studies. To understand how chiral nanoplatelets interact with biological systems, mammalian cell lines were exposed to them. Results showed that the achiral as well as the left- and right-handed biomimetic χ3 and ß12 borophene nanoplatelets have distinct interaction with the cellular membrane, and their internalization pathway differs with their chirality. By engineering optical, physical, and chemical properties, these chiral 2D nanomaterials could be applied successfully to tuning complex biological events and find applications in photonics, sensing, catalysis, and biomedicine.

Context-Responsive Nanoparticle Derived from Synthetic Zwitterionic Ionizable Phospholipids in Targeted CRISPR/Cas9 Therapy for Basal-like Breast Cancer.

The majority of triple negative breast cancers (TNBCs) are basal-like breast cancers (BLBCs), which tend to be more aggressive, proliferate rapidly, and have poor clinical outcomes. A key prognostic biomarker and regulator of BLBC is the Forkhead box C1 (FOXC1) transcription factor. However, because of its functional placement inside the cell nucleus and its structural similarity with other related proteins, targeting FOXC1 for therapeutic benefit, particularly for BLBC, continues to be difficult. We envision targeted nonviral delivery of CRISPR/Cas9 plasmid toward the efficacious knockdown of FOXC1. Keeping in mind the challenges associated with the use of CRISPR/Cas9 in vivo, including off-targeting modifications, and effective release of the cargo, a nanoparticle with context responsive properties can be designed for efficient targeted delivery of CRISPR/Cas9 plasmid. Consequently, we have designed, synthesized, and characterized a zwitterionic amino phospholipid-derived transfecting nanoparticle for delivery of CRISPR/Cas9. The construct becomes positively charged only at low pH, which encourages membrane instability and makes it easier for nanoparticles to exit endosomes. This has enabled effective in vitro and in vivo downregulation of protein expression and genome editing. Following this, we have used EpCAM aptamer to make the system targeted toward BLBC cell lines and to reduce its off-target toxicity. The in vivo efficacy, biodistribution, preliminary pharmacokinetics, and biosafety of the optimized targeted CRISPR nanoplatform is then validated in a rodent xenograft model. Overall, we have attempted to knockout the proto-oncogenic FOXC1 expression in BLBC cases by efficient delivery of CRISPR effectors via a context-responsive nanoparticle delivery system derived from a designer lipid derivative. We believe that the nonviral approach for in vitro and in vivo delivery of CRISPR/Cas9 targeted toward FOXC1, studied herein, will greatly emphasize the therapeutic regimen for BLBC.

Nanomedicine and nanobiotechnology in India.

Nanomedicine, an interdisciplinary field combining nanotechnology and medicine, has gained immense attention in recent years due to its potential in revolutionizing healthcare. India, being an emerging hub for scientific research and development, has made significant strides in nanomedicine research. This special issue is dedicated to the exciting research that are being conducted by the leading Indian scientists in various Indian institutions. This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Synthesis and Bioapplication of Emerging Nanomaterials of Hafnium.

A significant amount of progress in nanotechnology has been made due to the development of engineered nanoparticles. The use of metallic nanoparticles for various biomedical applications has been extensively investigated. Biomedical research is highly focused on them because of their inert nature, nanoscale structure, and similar size to many biological molecules. The intrinsic characteristics of these particles, including electronic, optical, physicochemical, and surface plasmon resonance, that can be altered by altering their size, shape, environment, aspect ratio, ease of synthesis, and functionalization properties, have led to numerous biomedical applications. Targeted drug delivery, sensing, photothermal and photodynamic therapy, and imaging are some of these. The promising clinical results of NBTXR3, a high-Z radiosensitizing nanomaterial derived from hafnium, have demonstrated translational potential of this metal. This radiosensitization approach leverages the dependence of energy attenuation on atomic number to enhance energy-matter interactions conducive to radiation therapy. High-Z nanoparticle localization in tumor issue differentially increases the effect of ionizing radiation on cancer cells versus nearby healthy ones and mitigates adverse effects by reducing the overall radiation burden. This principle enables material multifunctionality as contrast agents in X-ray-based imaging. The physiochemical properties of hafnium (Z = 72) are particularly advantageous for these applications. A well-placed K-edge absorption energy and high mass attenuation coefficient compared to elements in human tissue across clinical energy ranges leads to significant attenuation. Chemical reactivity allows for variety in nanoparticle synthesis, composition, and functionalization. Nanoparticles such as hafnium oxide exhibit excellent biocompatibility due to physiochemical inertness prior to incidence with ionizing radiation. Additionally, the optical and electronic properties are applicable in biosensing, optical component coatings, and semiconductors. The wide interest has prompted extensive research in design and synthesis to facilitate property fine-tuning. This review summarizes synthetic methods for hafnium-based nanomaterials and applications in therapy, imaging, and biosensing with a mechanistic focus. A discussion and future perspective section highlights clinical progress and elaborates on current challenges. By focusing on factors impacting applicational effectiveness and examining limitations this review aims to support researchers and expedite clinical translation of future hafnium-based nanomedicine.

Carbon Dots: From Synthesis to Unraveling the Fluorescence Mechanism.

Carbon dots (CDs) being a new type of carbon-based nanomaterial have attracted intensive interest from researchers owing to their excellent biophysical properties. CDs are a class of fluorescent carbon nanomaterials that have emerged as a promising alternative to traditional quantum dots and organic dyes in applications including bioimaging, sensing, and optoelectronics. CDs possess unique optical properties, such as tunable emission, facile synthesis, and low toxicity, making them attractive for many applications in biology, medicine, and environmental areas. The synthesis of CDs is achievable by a variety of methods, including bottom-up and top-down approaches, involving the use of different carbon sources and surface functionalization strategies. However, understanding the fluorescence mechanism of CDs remains a challenge. Various mechanistic models have been proposed to explain their origin of luminescence. This review summarizes the recent developments in the synthesis and functionalization of CDs and provides an overview of the current understanding of the fluorescence mechanism.

NanoLC-timsTOF-Assisted Analysis of Glycated Albumin in Diabetes-Affected Plasma and Tears.

Glycation is a spontaneous and nonenzymatic glycosylation. Glycated albumin (GA), which serves as an important biomarker in plasma in the diagnosis and characterization of diabetes, can be passively filtered from the plasma to tears. Tears are important targets for research in clinical diagnostics due to the ability to collect this biofluid noninvasively and repeatably. Therefore, the analysis of GA in tear film provides information for monitoring diabetes progression independent of blood pathologies. Due to the limited volume (1-5 µL) of natural tear film, we developed a small volume assay using a nano liquid chromatography-trapped ion mobility spectrometry-time-of-flight MS (nanoLC-timsTOF) platform for the analysis of glycated albumin in human plasma and tear films affected by diabetes. The peptides containing lysine 525, which is the main glycation site in GA, were relatively quantified and represented as the GA level. The results of the measurements showed that GA levels were significantly higher in diabetes-affected plasma and tears compared to controls with a p-value < 0.01. A strong correlation of glycated albumin levels was observed for the plasma and tear film in diabetes samples (Pearson coefficient 0.92 with a p-value 0.0012). Moreover, the number of GA glycation sites was significantly higher in diabetes-affected plasma and tear comparatively to controls. Among all the glycation sites in plasma albumin, the GA level quantified by lysine 136/137 had a strong correlation with more commonly used lysine 525, suggesting that lysine 136 /137 is an alternative diabetes biomarker in plasma. Overall, our findings demonstrate GA in tears as a biomarker for monitoring diabetes progression, highlighting new possibilities for quick and noninvasive diabetes detection and monitoring.

Diagnosis of COVID-19 with simultaneous accurate prediction of cardiac abnormalities from chest computed tomographic images.

COVID-19 has potential consequences on the pulmonary and cardiovascular health of millions of infected people worldwide. Chest computed tomographic (CT) imaging has remained the first line of diagnosis for individuals infected with SARS-CoV-2. However, differentiating COVID-19 from other types of pneumonia and predicting associated cardiovascular complications from the same chest-CT images have remained challenging. In this study, we have first used transfer learning method to distinguish COVID-19 from other pneumonia and healthy cases with 99.2% accuracy. Next, we have developed another CNN-based deep learning approach to automatically predict the risk of cardiovascular disease (CVD) in COVID-19 patients compared to the normal subjects with 97.97% accuracy. Our model was further validated against cardiac CT-based markers including cardiac thoracic ratio (CTR), pulmonary artery to aorta ratio (PA/A), and presence of calcified plaque. Thus, we successfully demonstrate that CT-based deep learning algorithms can be employed as a dual screening diagnostic tool to diagnose COVID-19 and differentiate it from other pneumonia, and also predicts CVD risk associated with COVID-19 infection.

Highly-Specific Single-Stranded Oligonucleotides and Functional Nanoprobes for Clinical Determination of Chlamydia Trachomatis and Neisseria Gonorrhoeae Infections.

Early detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is the key to controlling the spread of these bacterial infections. An important step in developing biosensors involves identifying reliable sensing probes against specific genetic targets for CT and NG. Here, the authors have designed single-stranded oligonucleotides (ssDNAs) targeting mutually conserved genetic regions of cryptic plasmid and chromosomal DNA of both CT and NG. The 5'- and 3'- ends of these ssDNAs are differentially functionalized with thiol groups and coupled with gold nanoparticles (AuNP) to develop absorbance-based assay. The AuNPs agglomerate selectively in the presence of its target DNA sequence and demonstrate a change in their surface plasmon resonance. The optimized assay is then used to detect both CT and NG DNA extracted from 60 anonymized clinical samples with a clinical sensitivity of ∼100%. The limit of detection of the assays are found to be 7 and 5 copies/µL for CT and NG respectively. Furthermore, it can successfully detect the DNA levels of these two bacteria without the need for DNA extraction and via a lateral flow-based platform. These assays thus hold the potential to be employed in clinics for rapid and efficient monitoring of sexually transmitted infections.

Synthesis of an enediyne carbon-allotrope surface for photo-thermal degradation of DNA.

The improper disposal of hospital waste products containing genetic materials poses a serious safety threat. We present herein an environmentally friendly technology using a graphene-based novel carbon-allotropic surface to remediate such wastes. The used carbon-allotrope is decorated with an enediyne (EDE-1) enriched aromatic pi-conjugated structure to create an efficient and active surface for cleaving DNA strands. Under controlled exposure of ultraviolet (UV) radiation and heat, the developed surface influences genetic degradation without disturbing the bacterial populations present downstream of the water treatment system. The designed material has been extensively characterized using physicochemical and biological tools. Our results indicate that this approach can possibly be introduced in large scale hospital waste disposal streams for remediating genetic hazards and thereby developing a portable self-contained system.

Biodegradable and switchable near-infrared fluorescent probes for hypoxia detection.

Aims: Among solid tumors, hypoxia is a common characteristic and responsible for chemotherapeutic resistance. Hypoxia-sensitive imaging probes are therefore essential for early tumor detection, growth monitoring and drug-response evaluation. Despite significant efforts, detecting hypoxic oxygen levels remains challenging. Materials & methods: This paper demonstrates the use of an amine-rich carbon dot probe functionalized with an imidazole group that exhibits reversible fluorescence switching in normoxic and hypoxic environments. Results & conclusion: We demonstrate the ability to emit near-infrared light only under hypoxic conditions. The probes are found to be biodegradable in the presence of human digestive enzymes such as lipase. Ex vivo tissue imaging experiments revealed promising near-infrared signals even at a depth of 5 mm for the probe under ex vivo imaging conditions.

Hypoxia is the state where oxygen is not adequately available at the tissue level and is the common cause of resistance toward chemotherapeutics. Hence, probes that can detect hypoxia are important in detecting early tumor progression. Here in this paper, we have developed a fluorescent probe which helps in determining normoxic and hypoxic environments. This probe emits near-infrared light only under hypoxic conditions. The phenomena have been established herein by extensive experiments.

Ensemble and single-particle level fluorescent fine-tuning of carbon dots via positional changes of amines toward "supervised" oral microbiome sensing.

Significance: Carbon dots (CDs) have attracted a host of research interest in recent years mainly due to their unique photoluminescence (PL) properties that make them applicable in various biomedical areas, such as imaging and image-guided therapy. However, the real mechanism underneath the PL is a subject of wide controversy and can be investigated from various angles. Aim: Our work investigates the effect of the isomeric nitrogen position as the precursor in the synthesis of CDs by shedding light on their photophysical properties on the single particles and ensemble level. Approach: To this end, we adopted five isomers of diaminopyridine (DAP) and urea as the precursors and obtained CDs during a hydrothermal process. The various photophysical properties were further investigated in depth by mass spectroscopy. CD molecular frontier orbital analyses aided us in justifying the fluorescence emission profile on the bulk level as well as the charge transfer processes. As a result of the varying fluorescent responses, we indicate that these particles can be utilized for machine learning (ML)-driven sensitive detection of oral microbiota. The sensing results were further supported by density functional theoretical calculations and docking studies. Results: The generating isomers have a significant effect on the overall photophysical properties at the bulk/ensembled level. On the single-particle level, although some of the photophysical properties such as average intensity remained the same, the overall differences in brightness, photo-blinking frequency, and bleaching time between the five samples were conceived. The various photophysical properties could be explained based on the different chromophores formed during the synthesis. Overall, an array of CDs was demonstrated herein to achieve ∼100% separation efficacy in segregating a mixed oral microbiome culture in a rapid (<0.5 h), high-throughput manner with superior accuracy. Conclusions: We have indicated that the PL properties of CDs can be regulated by the precursors' isomeric position of nitrogen. We emancipated this difference in a rapid method relying on ML algorithms to segregate the dental bacterial species as biosensors.

Binding-Induced Folding of DNA Oligonucleotides Targeted to the Nucleocapsid Gene Enables Electrochemical Sensing of SARS-CoV-2.

In the wake of the COVID-19 pandemic, millions of confirmed cases and deaths have been reported around the world. COVID-19 spread can be slowed and eventually stopped by a rapid test to diagnose positive cases of the disease on the spot. It is still important to test for COVID-19 quickly regardless of the availability of the vaccine. Using the binding-induced folding principle, we developed an electrochemical test for detecting SARS-CoV-2 with no RNA extraction or nucleic acid amplification. The test showed high sensitivity with a limit of detection of 2.5 copies/µL. An electrode mounted with a capture probe and a portable potentiostat are used to conduct the test. To target the N-gene of SARS-CoV-2, a highly specific oligo-capturing probe was used. Based on the binding-induced "folding" principle, the sensor detects binding between the oligo and RNA. When the target is absent, the capture probe tends to form a hairpin as a secondary structure, retaining the redox reporter close to the surface. This can be seen as a large anodic and cathodic peak current. When the target RNA is present, the hairpin structure will open to hybridize with its complementary sequence, causing the redox reporter to pull away from the electrode. Consequently, the anodic/cathodic peak currents are reduced, indicating the presence of the SARS-CoV-2 genetic material. Validation of the test performance was performed using 122 COVID-19 clinical samples (55 positives and 67 negatives) and benchmarked to the gold standard reverse transcription-polymerase chain reaction (RT-PCR) test. As a result of our test, the accuracy, sensitivity, and specificity have been measured at 98.4%, 98.2%, and 98.5%, respectively.

A narrative review on the role of carbon nanoparticles in oncology.

The lymphatic system is the first site of metastasis for most tumors and is a common reason for the failure of cancer therapy. The lymphatic system's anatomical properties make it difficult to deliver chemotherapy agents at therapeutic concentrations while avoiding systemic toxicity. Carbon nanoparticles offer a promising alternative for identifying and transporting therapeutic molecules. The larger diameter of lymphatic vessels compared to the diameter of blood vessels, allows carbon nanoparticles to selectively enter the lymphatic system once administered subcutaneously. Carbon nanoparticles stain tumor-draining lymph nodes black following intratumoral injection, making them useful in sentinel lymph node mapping. Drug-loaded carbon nanoparticles allow higher concentrations of chemotherapeutics to accumulate in regional lymph nodes while decreasing plasma drug accumulation. The use of carbon nanoparticles for chemotherapy delivery has been associated with lower mortality, fewer histopathology changes in vital organs, and lower serum concentrations of hepatocellular enzymes. This review will focus on the ability of carbon nanoparticles to target the lymphatics as well as their current and potential applications in sentinel lymph node mapping and oncology treatment regimens. This article is categorized under: Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery.

Use of acidic nanoparticles to rescue macrophage lysosomal dysfunction in atherosclerosis.

Dysfunction in the macrophage lysosomal system including reduced acidity and diminished degradative capacity is a hallmark of atherosclerosis, leading to blunted clearance of excess cellular debris and lipids in plaques and contributing to lesion progression. Devising strategies to rescue this macrophage lysosomal dysfunction is a novel therapeutic measure. Nanoparticles have emerged as an effective platform to both target specific tissues and serve as drug delivery vehicles. In most cases, administered nanoparticles are taken up non-selectively by the mononuclear phagocyte system including monocytes/macrophages leading to the undesirable degradation of cargo in lysosomes. We took advantage of this default route to target macrophage lysosomes to rectify their acidity in disease states such as atherosclerosis. Herein, we develop and test two commonly used acidic nanoparticles, poly-lactide-co-glycolic acid (PLGA) and polylactic acid (PLA), both in vitro and in vivo. Our results in cultured macrophages indicate that the PLGA-based nanoparticles are the most effective at trafficking to and enhancing acidification of lysosomes. PLGA nanoparticles also provide functional benefits including enhanced lysosomal degradation, promotion of macroautophagy/autophagy and protein aggregate removal, and reduced apoptosis and inflammasome activation. We demonstrate the utility of this system in vivo, showing nanoparticle accumulation in, and lysosomal acidification of, macrophages in atherosclerotic plaques. Long-term administration of PLGA nanoparticles results in significant reductions in surrogates of plaque complexity with reduced apoptosis, necrotic core formation, and cytotoxic protein aggregates and increased fibrous cap formation. Taken together, our data support the use of acidic nanoparticles to rescue macrophage lysosomal dysfunction in the treatment of atherosclerosis.Abbreviations: BCA: brachiocephalic arteries; FACS: fluorescence activated cell sorting; FITC: fluorescein-5-isothiocyanatel; IL1B: interleukin 1 beta; LAMP: lysosomal associated membrane protein; LIPA/LAL: lipase A, lysosomal acid type; LSDs: lysosomal storage disorders; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFI: mean fluorescence intensity; MPS: mononuclear phagocyte system; PEGHDE: polyethylene glycol hexadecyl ether; PLA: polylactic acid; PLGA: poly-lactide-co-glycolic acid; SQSTM1/p62: sequestosome 1.

Diagnostic Approaches For COVID-19: Lessons Learned and the Path Forward.

Coronavirus disease 2019 (COVID-19) is a transmitted respiratory disease caused by the infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although humankind has experienced several outbreaks of infectious diseases, the COVID-19 pandemic has the highest rate of infection and has had high levels of social and economic repercussions. The current COVID-19 pandemic has highlighted the limitations of existing virological tests, which have failed to be adopted at a rate to properly slow the rapid spread of SARS-CoV-2. Pandemic preparedness has developed as a focus of many governments around the world in the event of a future outbreak. Despite the largely widespread availability of vaccines, the importance of testing has not diminished to monitor the evolution of the virus and the resulting stages of the pandemic. Therefore, developing diagnostic technology that serves as a line of defense has become imperative. In particular, that test should satisfy three criteria to be widely adopted: simplicity, economic feasibility, and accessibility. At the heart of it all, it must enable early diagnosis in the course of infection to reduce spread. However, diagnostic manufacturers need guidance on the optimal characteristics of a virological test to ensure pandemic preparedness and to aid in the effective treatment of viral infections. Nanomaterials are a decisive element in developing COVID-19 diagnostic kits as well as a key contributor to enhance the performance of existing tests. Our objective is to develop a profile of the criteria that should be available in a platform as the target product. In this work, virus detection tests were evaluated from the perspective of the COVID-19 pandemic, and then we generalized the requirements to develop a target product profile for a platform for virus detection.

A Machine Learning Framework for Detecting COVID-19 Infection Using Surface-Enhanced Raman Scattering.

In this study, we explored machine learning approaches for predictive diagnosis using surface-enhanced Raman scattering (SERS), applied to the detection of COVID-19 infection in biological samples. To do this, we utilized SERS data collected from 20 patients at the University of Maryland Baltimore School of Medicine. As a preprocessing step, the positive-negative labels are obtained using Polymerase Chain Reaction (PCR) testing. First, we compared the performance of linear and nonlinear dimensionality techniques for projecting the high-dimensional Raman spectra to a low-dimensional space where a smaller number of variables defines each sample. The appropriate number of reduced features used was obtained by comparing the mean accuracy from a 10-fold cross-validation. Finally, we employed Gaussian process (GP) classification, a probabilistic machine learning approach, to correctly predict the occurrence of a negative or positive sample as a function of the low-dimensional space variables. As opposed to providing rigid class labels, the GP classifier provides a probability (ranging from zero to one) that a given sample is positive or negative. In practice, the proposed framework can be used to provide high-throughput rapid testing, and a follow-up PCR can be used for confirmation in cases where the model's uncertainty is unacceptably high.

In Situ Surface-Directed Assembly of 2D Metal Nanoplatelets for Drug-Free Treatment of Antibiotic-Resistant Bacteria.

The development of antibiotic resistance among bacterial strains is a major global public health concern. To address this, drug-free antibacterial approaches are needed. Copper surfaces have long been known for their antibacterial properties. In this work, a one-step surface modification technique is used to assemble 2D copper chloride nanoplatelets directly onto copper surfaces such as copper tape, transmission electron microscopy (TEM) grids, electrodes, and granules. The nanoplatelets are formed using copper ions from the copper surfaces, enabling their direct assembly onto these surfaces in a one-step process that does not require separate nanoparticle synthesis. The synthesis of the nanoplatelets is confirmed with TEM, scanning electron microscopy, energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). Antibacterial properties of the Cu nanoplatelets are demonstrated in multidrug-resistant (MDR) Escherichia coli, MDR Acinetobacter baumannii, MDR Staphylococcus aureus, E. coli, and Streptococcus mutans. Nanoplatelets lead to a marked improvement in antibacterial properties compared to the copper surfaces alone, affecting bacterial cell morphology, preventing bacterial cell division, reducing their viability, damaging bacterial DNA, and altering protein expression. This work presents a robust method to directly assemble copper nanoplatelets onto any copper surface to imbue it with improved antibacterial properties.

Small Molecule NIR-II Dyes for Switchable Photoluminescence via Host -Guest Complexation and Supramolecular Assembly with Carbon Dots.

Small molecular NIR-II dyes are highly desirable for various biomedical applications. However, NIR-II probes are still limited due to the complex synthetic processes and inadequate availability of fluorescent core. Herein, the design and synthesis of three small molecular NIR-II dyes are reported. These dyes can be excited at 850-915 nm and emitted at 1280-1290 nm with a large stokes shift (≈375 nm). Experimental and computational results indicate a 2:1 preferable host-guest assembly between the cucurbit[8]uril (CB) and dye molecules. Interestingly, the dyes when self-assembled in presence of CB leads to the formation of nanocubes (≈200 nm) and exhibits marked enhancement in fluorescence emission intensity (Switch-On). However, the addition of red carbon dots (rCDots, ≈10 nm) quenches the fluorescence of these host-guest complexes (Switch-Off) providing flexibility in the user-defined tuning of photoluminescence. The turn-ON complex found to have comparable quantum yield to the commercially available near-infrared fluorophore, IR-26. The aqueous dispersibility, cellular and blood compatibility, and NIR-II bioimaging capability of the inclusion complexes is also explored. Thus, a switchable fluorescence behavior, driven by host-guest complexation and supramolecular self-assembly, is demonstrated here for three new NIR-II dyes.

Probing the mutation independent interaction of DNA probes with SARS-CoV-2 variants through a combination of surface-enhanced Raman scattering and machine learning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has been characterized by the emergence of sets of mutations impacting the virus characteristics, such as transmissibility and antigenicity, presumably in response to the changing immune profile of the human population. The presence of mutations in the SARS-CoV-2 virus can potentially impact therapeutic and diagnostic test performances. We design and develop here a unique set of DNA probes i.e., antisense oligonucleotides (ASOs) which can interact with genetic sequences of the virus irrespective of its ongoing mutations. The probes, developed herein, target a specific segment of the nucleocapsid phosphoprotein (N) gene of SARS-CoV-2 with high binding efficiency which do not mutate among the known variants. Further probing into the interaction profile of the ASOs reveals that the ASO-RNA hybridization remains unaltered even for a hypothetical single point mutation at the target RNA site and diminished only in case of the hypothetical double or triple point mutations. The mechanism of interaction among the ASOs and SARS-CoV-2 RNA is then explored with a combination of surface-enhanced Raman scattering (SERS) and machine learning techniques. It has been observed that the technique, described herein, could efficiently discriminate between clinically positive and negative samples with ∼100% sensitivity and ∼90% specificity up to 63 copies/mL of SARS-CoV-2 RNA concentration. Thus, this study establishes N gene targeted ASOs as the fundamental machinery to efficiently detect all the current SARS-CoV-2 variants regardless of their mutations.

Hitchhiking probiotic vectors to deliver ultra-small hafnia nanoparticles for 'Color' gastrointestinal tract photon counting X-ray imaging.

Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of contrast agents and drugs mediated by nanoparticles due to its harsh environment. Herein, we overcame this barrier by designing orally ingestible probiotic vectors for 'hitchhiking' ultrasmall hafnia (HfO2) (∼1-2 nm) nanoparticles. The minute-made synthesis of these nanoparticles is accomplished through a simple reduction reaction. These nanoparticles were incubated with probiotic bacteria with potential health benefits and were non-specifically taken up due to their small size. Subsequently, the bacteria were lyophilized and packed into a capsule to be administered orally as the radiopaque contrast agents for delineating the GI features. These nano-bio-hybrid entities could successfully be utilized as contrast agents in vivo in the conventional and multispectral computed tomography (CT). We demonstrated in 'color' the accumulated nanoparticles using advanced detectors of the photon counting CT. The enhanced nano-bio-interfacing capability achieved here can circumvent traditional nanoparticle solubility and delivery problems while offering a patient friendly approach for GI imaging to replace the currently practiced barium meal.