Surface ligand influences the Cu nanoclusters as a dual sensing optical probe for localized pH environment and fluoride ion

Functional metal nanomaterials, especially in the nanocluster (NC) size regime, with strong fluorescence, aqueous colloidal stability, and low toxicity, necessitate their application potential in biology and environmental science. Here, we successfully report a simple cost-effective method for red-/green-color-emitting protein/amino-acid-mediated Cu NCs in an aqueous medium. As-synthesized Cu NCs were characterized through UV-Vis absorption spectroscopy, fluorescence spectroscopy, time-resolved photoluminescence, dynamic light scattering, zeta potential, transmission electron microscopy and X-ray photoelectron spectroscopy. The optical properties of both Cu NCs responded linearly to the variation in pH in the neutral and alkaline ranges, and a robust pH reversible nature (between pH 7 and 11) was observed that could be extended to rapid, localized pH sensor development. However, a contrasting pH response nature between protein-Cu NCs and amino acid-Cu NCs was recorded. The alteration in protein secondary structure and strong binding nature of the surfactants were suggested to explain this behavior. Furthermore, we investigated their use as an efficient optical probe for fluoride ion detection. The limit of detection for protein-Cu NCs is 6.74 µM, whereas the limit of detection for amino acid-Cu NCs is 4.67 µM. Thus, it is anticipated that ultrasmall Cu NCs will exhibit promise in biological and environmental sensing applications.Published versionSC thank SRM University, AP research funding (SRMAP/URG/E&PP/2022-23/014) for financial support

Positron emission tomographic imaging in drug discovery

Positron emission tomography (PET) is an extensively used nuclear functional imaging technique, especially for central nervous system (CNS) and oncological disorders. Currently, drug development is a lengthy and costly pursuit. Imaging with PET radiotracers could be an effective way to hasten drug discovery and advancement, because it facilitates the monitoring of key facets, such as receptor occupancy quantification, drug biodistribution, pharmacokinetic (PK) analyses, validation of target engagement, treatment monitoring, and measurement of neurotransmitter concentrations. These parameters demand careful analyses for the robust appraisal of newly formulated drugs during preclinical and clinical trials. In this review, we discuss the usage of PET imaging in radiopharmaceutical development; drug development approaches with PET imaging; and PET developments in oncological and cardiac drug discovery.Nanyang Technological UniversityAuthors acknowledge support from Lee Kong Chian School of Medicine, NTU Austrian Institute of Technology and Medical University of Vienna internal grant (NAM/15006), the LKC Medicine Imaging Probe Development Platform, Singapore, and the Cognitive Neuroimaging Centre (CONIC) at Nanyang Technological University, Singapore

The Multifarious Applications of Copper Nanoclusters in Biosensing and Bioimaging and Their Translational Role in Early Disease Detection

Nanoclusters possess an ultrasmall size, amongst other favorable attributes, such as a high fluorescence and long-term colloidal stability, and consequently, they carry several advantages when applied in biological systems for use in diagnosis and therapy. Particularly, the early diagnosis of diseases may be facilitated by the right combination of bioimaging modalities and suitable probes. Amongst several metallic nanoclusters, copper nanoclusters (Cu NCs) present advantages over gold or silver NCs, owing to their several advantages, such as high yield, raw abundance, low cost, and presence as an important trace element in biological systems. Additionally, their usage in diagnostics and therapeutic modalities is emerging. As a result, the fluorescent properties of Cu NCs are exploited for use in optical imaging technology, which is the most commonly used research tool in the field of biomedicine. Optical imaging technology presents a myriad of advantages over other bioimaging technologies, which are discussed in this review, and has a promising future, particularly in early cancer diagnosis and imaging-guided treatment. Furthermore, we have consolidated, to the best of our knowledge, the recent trends and applications of copper nanoclusters (Cu NCs), a class of metal nanoclusters that have been gaining much traction as ideal bioimaging probes, in this review. The potential modes in which the Cu NCs are used for bioimaging purposes (e.g., as a fluorescence, magnetic resonance imaging (MRI), two-photon imaging probe) are firstly delineated, followed by their applications as biosensors and bioimaging probes, with a focus on disease detection

An in vivo study of a rat fluid-percussion-induced traumatic brain injury model with [¹¹C]PBR28 and [¹⁸F]flumazenil PET imaging

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [¹¹C]PBR28 and [¹⁸F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [¹¹C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [¹⁸F]flumazenil is a radioligand for GABAᴀ-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [¹¹C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [¹⁸F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [¹¹C]PBR28 and [¹⁸F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.Nanyang Technological UniversityPublished versionAuthors acknowledge the support from the Lee Kong Chian School of Medicine, Nanyang Technological University (NTU) for a Start-Up Grant to B.G., and for the NTU-Austrian Institute of Technology-Medical University of Vienna Grant for Advanced Biomedical Imaging (NAM/15005), the LKCMedicine Imaging Probe Dev. Platform, Singapore and the Cognitive Neuroimaging Centre (CONIC) at Nanyang Technological University, Singapore

Potential impact of various surface ligands on the cellular uptake and biodistribution characteristics of red, green, and blue emitting Cu nanoclusters

Surface functionalization has a prominent influence on tuning/manipulating the physicochemical properties of nanometer scaled materials. Ultrasmall sized nanoclusters with very few atoms have received enormous attention due to their bright fluorescence, biocompatibility, lower toxicity, good colloidal stability and strong photostability. These properties make them suitable for diagnostic applications. In this work, we intend to study the effect of surface functional ligands on their biodistribution both in vitro and in vivo organelle systems for bioimaging applications.Published versionS. C. acknowledges the financial support from University Grant Commission-Department of Atomic Energy (UGC-DAE) Consortium for Scientific Research, (UGC-DAE-CRS/2021-22/02/513) and Science and Engineering Research Board (SERB) under State University Research Excellence (SUR/2022/001424)

Whole-genome sequencing of Aspergillus terreus species complex

Aspergillus terreus species complex is an opportunistic fungal pathogen increasingly implicated in invasive infection, as well as chronic respiratory disease. Currently, an understanding of A. terreus pathogenicity is impeded by a limited number of whole-genome sequences of this fungal pathogen. We here describe a high-quality whole-genome assembly of European A. terreus clinical isolate M6925, derived by single-molecule real-time sequencing with short-read polishing