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 GABAA-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.
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.
Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders that is implicated in aging populations. As numerous developed nations are experiencing progressively aging populations today, there is a heightened propensity for the occurrence of PD cases. Alpha-synuclein (α-syn) aggregation has been considered to be the pivotal mechanism leading to PD pathogenesis. Thus, early diagnostic and therapeutic strategies targeting the misfolded α-syn protein can potentially improve the prognosis of PD. With rapid advancements in nanotechnology in the last decade, effective solutions to various neurodegenerative and oncological diseases have been suggested. This review will explore the current innovations in nanotechnology that target the α-syn aggregation pathway, and reinstate the promise they hold as effective early diagnostic and therapeutic solutions to PD.
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