The Influence of Size and Chemical Composition of Silver and Gold Nanoparticles on in vivo Toxicity with Potential Applications to Central Nervous System Diseases

Ye D., Luan J., Pang H., Yang Y., Nazeri A., Rubin J.B., Chen H.

Focused ultrasound-mediated intranasal (FUSIN) delivery is a recently proposed technique that bypasses the blood-brain barrier to achieve noninvasive and localized brain drug delivery. The goal of this study was to characterize FUSIN drug delivery outcome in mice with regard to its dependency on several critical experimental factors, including the time interval between IN administration and FUS sonication (Tlag1), the FUS pressure, and the time for sacrificing the mice post-FUS (Tlag2). Wild-type mice were treated by FUSIN delivery of near-infrared fluorescent dye-labeled bovine serum albumin (800CW-BSA, used as a model agent). 800CW-BSA was intranasally administered to the mice in vivo, followed by intravenous injection of microbubbles and FUS sonication at the brainstem. Fluorescence imaging of ex vivo mouse brain slices was used to quantify the delivery outcomes of 800CW-BSA. Major organs, along with the nasal tissue and trigeminal nerve, were harvested to assess the biodistribution of 800CW-BSA. The delivery outcome of 800CW-BSA was the highest at the brainstem when Tlag1 was 0.5 h, which was on average 24.5-fold, 5.4-fold, and 21.6-fold higher than those of the IN only, Tlag1 = 1.5 h, and Tlag1 = 4.0 h, respectively. The FUSIN delivery outcome at the lowest pressure level, 0.43 MPa, was on average 1.8-fold and 3.7-fold higher than those at 0.56 MPa and 0.70 MPa, respectively. The mean concentration of 800CW-BSA in the brainstem after FUSIN delivery decreased from 0.5 h to 4.0 h post-FUS. The accumulation of 800CW-BSA was low in the heart, lung, spleen, kidneys, and liver, but high in the stomach and intestines. This study revealed the unique characteristics of FUSIN as a noninvasive, efficient, and localized brain drug delivery technique.

Zhang X., Li Y., Hu Y.

In this study, we showed the use of aqueous extract of N. khasiana leaf as a reducing and stabilizing agent for the synthesis of AgNPs and assessed their therapeutic potential in sporadic AD model rats produced by intracerebroventricular injection of streptozotocin (i.c.v.–STZ). Different spectroscopic and microscopic methods were used to characterize the as-prepared AgNPs. XRD pattern showed the formation of face centered cubic (FCC) crystalline AgNPs. In addition, FTIR studies revealed the capping of N. khasiana leaf extract polyphenols onto the surface of AgNPs. Furthermore, AgNPs prevented the effect of deficits in recognition and spatial memory of STZ induced diabetic rats. The results of Barnes Maze test revealed that 48 h STZ + AgNPs and Sham alone treated groups displayed a decrease in the time used to detect the escape hole on the 5th day of training. Also, the object recognition tests suggested that Sham + AgNPs 48 h, STZ + AgNPs 48 h and Sham alone groups consumed more time in recognizing new object on the 2nd day, whereas, STZ group identified both the objects at equal time indicating the ability of AgNPs in preventing this damage impaired performance of object recognition. Further these results concluded that the prepared AgNPs could be considered as a potential candidate for the treatment of Alzheimer's disease.

Gallardo-Toledo E., Tapia-Arellano A., Celis F., Sinai T., Campos M., Kogan M.J., Sintov A.C.

ANID, Ministry of Science, Chile 21151400 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1170929 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDAP 15130011

Al-Doaiss A.A., Jarrar Q., Alshehri M., Jarrar B.

Silver nanoparticles (Ag NPs) are widely used in nanomedicine, pharmaceutical products, industry and other consumer products owing to their unique physiochemical properties with probable potential risk to human health and the ecosystems. The aim of this work was to investigate the in-life morphological effects, biochemical, histological and histochemical alterations that might be induced by variable sizes of Ag NPs in hepatic, renal and testicular tissues with the hypothesis that variable sizes of nano-Ag could induce variable effects in the vital organs. Five groups of adult healthy male mice (BALB/C) were exposed to 35 intraperitoneal injections of Ag NPs (1 mg/kg bw) using five different particle sizes (10, 20, 40, 60 and 100 nm). All mice were subjected to in-life morphometric, biochemical, histological and histochemical analysis. The findings demonstrated that Ag NPs could induce alterations in the average body weight gain, food consumption, water intake and organ indices. In addition, these NPs significantly altered hepatic and renal biomarkers. Moreover, Ag NPs produced ground glass hepatocyte cytoplasm, with mitotic activity, nuclear alterations, degeneration, glycogen depletion and inflammatory cells infiltration in the liver. The kidneys of treated mice exhibited proximal renal tubules degeneration, distal renal tubules regeneration, glomerular shrinkage, Bowman’s capsule thickening and interstitial inflammation. The testicular tissues demonstrated spermatocyte sloughing and spermatid giant cell formation. The findings together indicated that Ag NPs could interact with the anatomical structures of the liver, kidney and testis in ways that could induce injury. In addition, the results indicated that smaller Ag NPs posed a greater potential risk than the larger ones, which might be associated with their behaviour, dissolution rate, bioavailability and their probable variable toxicokinetics.

Odatsu T., Kuroshima S., Sato M., Takase K., Valanezhad A., Naito M., Sawase T.

Peri-implantitis is an inflammatory disease with a relevant focus on the long-term success of dental implants and implant-supported prostheses. The present study focuses on the antibacterial effect of the silver nanoparticle and investigated the suppression of dental plaque adhesion on implant abutment and/or superstructure by micro-wave assistant nanosilver coating in vivo and in vitro. Nanosilver coating on pure titanium was prepared by microwave-assisted synthesis, and characterized by scanning electron microscopy and energy-dispersive X-ray spectroscopy. In vitro studies were conducted to analyze biocompatibility using MTS assay and fluorescence microscopy with human gingival fibroblasts to evaluate antibacterial activity. During the in vivo study, nanosilver coating was applied to the healing abutments, and the prevention of plaque accumulation on nanosilver coating was confirmed by a split-mouth randomized clinical trial. The aggregation of nano-sized particles was found on the titanium surface with an antibacterial effect. The coating had no cytotoxic effect on human gingival fibroblasts. The result of the clinical trial showed that the coating suppressed the dental plaque adhesion on the healing abutments. Nanosilver coating is a promising material with antibacterial properties and can be used for implant abutments and prostheses for preventing peri-implantitis.

Ferdous Z., Nemmar A.

Engineered nanomaterials (ENMs) have gained huge importance in technological advancements over the past few years. Among the various ENMs, silver nanoparticles (AgNPs) have become one of the most explored nanotechnology-derived nanostructures and have been intensively investigated for their unique physicochemical properties. The widespread commercial and biomedical application of nanosilver include its use as a catalyst and an optical receptor in cosmetics, electronics and textile engineering, as a bactericidal agent, and in wound dressings, surgical instruments, and disinfectants. This, in turn, has increased the potential for interactions of AgNPs with terrestrial and aquatic environments, as well as potential exposure and toxicity to human health. In the present review, after giving an overview of ENMs, we discuss the current advances on the physiochemical properties of AgNPs with specific emphasis on biodistribution and both in vitro and in vivo toxicity following various routes of exposure. Most in vitro studies have demonstrated the size-, dose- and coating-dependent cellular uptake of AgNPs. Following NPs exposure, in vivo biodistribution studies have reported Ag accumulation and toxicity to local as well as distant organs. Though there has been an increase in the number of studies in this area, more investigations are required to understand the mechanisms of toxicity following various modes of exposure to AgNPs.

Yin P., Li H., Ke C., Cao G., Xin X., Hu J., Cai X., Li L., Liu X., Du B.

Pannerselvam B., Devanathadesikan V., Alagumuthu T.S., Kanth S.V., Pudupalayam Thangavelu K.

Nanomedicine is an interdisciplinary approach that involves toxicology and other medicinal applications. Gold nanoparticles (AuNPs) may serve as a promising model to address the size and shape-dependent biological response because they show good biocompatibility. This study is to prepare phytosynthesis AuNPs from ten different Cassia sp. Among them, the aqueous leaf extract of C. roxburghii produced greater efficient and stable AuNPs. The AuNPs were optimised for different physicochemical conditions. Highly stable AuNPs were synthesised at pH 7.0, 37°C, 1.0 ml of C. roxburghii leaf extract and 1.0 mM concentration of HAuCl4 with the particle size of ∼50 nm and these AuNPs were stable up to 12 months. To determine the safety profile of AuNPs in-vivo, the nanoparticles were injected intravenously into male Wistar albino rats in varying dosages. The authors noticed no significant difference in body weights, haematological and biochemical parameters and the histopathological sections of all vital organs. Highest accumulation was seen in spleen and least in brain. The authors' results show that the AuNPs were biocompatible and did not produce any adverse or abnormalities in-vivo. The implications of the bioaccumulation of AuNPs need to be further studied to rule out any adverse effects on long-term exposure.

Khoobchandani M., Katti K.K., Karikachery A.R., Thipe V.C., Srisrimal D., Dhurvas Mohandoss D.K., Darshakumar R.D., Joshi C.M., Katti K.V.

I R., MJ S., R G., FJ D.L., MJ B., MA M.

Infections caused by HSV-1 and their typical outbreaks invading the nervous system have been related to neurodegenerative diseases. HSV-1 infection may deregulate the balance between the amyloidogenic and non-amyloidogenic pathways, raising the accumulation of amyloid-β peptides, one of the hallmarks in the neurodegenerative diseases. An effective treatment against both, HSV-1 infections and neurodegeneration, is a major therapeutic target. Therefore, gold nanoparticles (NPAus) have been previously studied in immunotherapy, cancer and cellular disruptions with very promising results. Our study demonstrates that a new NPAus family inhibits the HSV-1 infection in a neural-derived SK-N-MC cell line model and that this new NPAus reduces the HSV-1-induced β-secretase activity, as well as amyloid-β accumulation in SK-APP-D1 modifies cell line. We demonstrated that NPAuG3-S8 crosses the blood-brain barrier (BBB) and does not generate cerebral damage to in vivo CD1 mice model. The NPAuG3-S8 could be a promising treatment against neuronal HSV-1 infections and neuronal disorders related to the Aβ peptides.

Carneiro P., Morais S., Pereira M.C.

Alzheimer’s disease (AD) is an incurable and highly debilitating condition characterized by the progressive degeneration and/or death of nerve cells, which leads to manifestation of disabilities in cognitive functioning. In recent years, the development of biosensors for determination of AD’s main biomarkers has made remarkable progress, particularly based on the tremendous advances in nanoscience and nanotechnology. The unique and outstanding properties of nanomaterials (such as graphene, carbon nanotubes, gold, silver and magnetic nanoparticles, polymers and quantum dots) have been contributing to enhance the electrochemical and optical behavior of transducers while offering a suitable matrix for the immobilization of biological recognition elements. Therefore, optical and electrochemical immuno- and DNA-biosensors with higher sensitivity, selectivity and longer stability have been reported. Nevertheless, strategies based on the detection of multiple analytes still need to be improved, as they will play a crucial role in minimizing misdiagnosis. This review aims to provide insights into the conjugation of nanomaterials with different transducers highlighting their crucial role in the construction of biosensors for detection of AD main biomarkers.

Sawicki K., Czajka M., Matysiak-Kucharek M., Fal B., Drop B., Męczyńska-Wielgosz S., Sikorska K., Kruszewski M., Kapka-Skrzypczak L.

Abstract Metallic nanoparticles due to their small size and unique physico-chemical characteristics have found excellent applications in various branches of industry and medicine. Therefore, for many years a growing interest has been observed among the scientific community in the improvement of our understanding of the impact of nanoparticles on the living organisms, especially on humans. Considering the delicate structure of the central nervous systemit is one of the organs most vulnerable to the adverse effects of metallic nanoparticles. For that reason, it is important to identify the modes of exposure and understand the mechanisms of the effect of nanoparticles on neuronal tissue. In this review, an attempt is undertaken to present current knowledge about metallic nanoparticles neurotoxicity based on the selected scientific publications. The route of entry of nanoparticles is described, as well as their distribution, penetration through the cell membrane and the blood-brain barrier. In addition, a study on the neurotoxicity in vitro and in vivo is presented, as well as some of the mechanisms that may be responsible for the negative effects of metallic nanoparticles on the central nervous system. Graphical abstract: This review summarizes the current knowledge on the toxicity of metallic NPs in the brain and central nervous system of the higher vertebrates.

Sukumar U.K., Bose R.J., Malhotra M., Babikir H.A., Afjei R., Robinson E., Zeng Y., Chang E., Habte F., Sinclair R., Gambhir S.S., Massoud T.F., Paulmurugan R.

The prognosis for glioblastoma (GBM) remains depressingly low. The biological barriers of the brain present a major challenge to achieving adequate drug concentrations for GBM therapy. To address this, we explore the potential of the nose-to-brain direct transport pathway to bypass the blood-brain barrier, and to enable targeted delivery of theranostic polyfunctional gold-iron oxide nanoparticles (polyGIONs) surface loaded with therapeutic miRNAs (miR-100 and antimiR-21) to GBMs in mice. These nanoformulations would thus allow presensitization of GBM cells to the systemically delivered chemotherapy drug temozolomide (TMZ), as well as in vivo multimodality molecular and anatomic imaging of nanoparticle delivery, trafficking, and treatment effects. First, we synthesized GIONs coated with β-cyclodextrin-chitosan (CD-CS) hybrid polymer, and co-loaded with miR-100 and antimiR-21. Then we decorated their surface with PEG-T7 peptide using CD-adamantane host-guest chemistry. The resultant polyGIONs showed efficient miRNA loading with enhanced serum stability. We characterized them for particle size, PDI, polymer functionalization , charge and release using dynamic light scattering analysis, TEM and qRT-PCR. For in vivo intranasal delivery, we used U87-MG GBM cell-derived orthotopic xenograft models in mice. Intranasal delivery resulted in efficient accumulation of Cy5-miRNAs in mice treated with T7-targeted polyGIONs, as demonstrated by in vivo optical fluorescence and MR imaging. We measured the therapeutic response of these FLUC-EGFP labelled U87-MG GBMs using bioluminescence imaging. Overall, there was a significant increase in survival of mice co-treated with T7-polyGIONs loaded with miR-100/antimiR-21 plus systemic TMZ, compared to the untreated control group, or the animals receiving non-targeted polyGIONs-miR-100/antimiR-21, or TMZ alone. Once translated clinically, this novel theranostic nanoformulation and its associated intranasal delivery strategy will have a strong potential to potentiate the effects of TMZ treatment in GBM patients.

Nicolson F., Andreiuk B., Andreou C., Hsu H., Rudder S., Kircher M.F.

Rationale: The goal of imaging tumors at depth with high sensitivity and specificity represents a significant challenge in the field of biomedical optical imaging. 'Surface enhanced Raman scattering' (SERS) nanoparticles (NPs) have been employed as image contrast agents and can be used to specifically target cells in vivo. By tracking their unique "fingerprint" spectra, it becomes possible to determine their precise location. However, while the detection of SERS NPs is very sensitive and specific, conventional Raman spectroscopy imaging devices are limited in their inability to probe through tissue depths of more than a few millimetres, due to scattering and absorption of photons by biological tissues. Here, we combine the use of "Spatially Offset Raman spectroscopy" (SORS) with that of "surface-enhanced resonance Raman spectroscopy" (SERRS) in a technique known as "surface enhanced spatially offset resonance Raman spectroscopy" (SESO(R)RS) to image deep-seated glioblastoma multiforme (GBM) tumors in vivo in mice through the intact skull. Methods: A SORS imaging system was built in-house. Proof of concept SORS imaging was achieved using a PTFE-skull-tissue phantom. Imaging of GBMs in the RCAS-PDGF/N-tva transgenic mouse model was achieved through the use of gold nanostars functionalized with a resonant Raman reporter to create SERRS nanostars. These were then encapsulated in a thin silica shell and functionalized with a cyclic-RGDyK peptide to yield integrin-targeting SERRS nanostars. Non-invasive in vivo SORS image acquisition of the integrin-targeted nanostars was then performed in living mice under general anesthesia. Conventional non-SORS imaging was used as a direct comparison. Results: Using a low power density laser, GBMs were imaged via SESORRS in mice (n = 5) and confirmed using MRI and histopathology. The results demonstrate that via utilization of the SORS approach, it is possible to acquire clear and distinct Raman spectra from deep-seated GBMs in mice in vivo through the skull. SESORRS images generated using classical least squares outlined the tumors with high precision as confirmed via MRI and histology. Unlike SESORRS, conventional Raman imaging of the same areas did not provide a clear delineation of the tumor. Conclusion: To the best of our knowledge this is the first report of in vivo SESO(R)RS imaging. In a relevant brain tumor mouse model we demonstrate that this technique can overcome the limitations of conventional Raman imaging with regards to penetration depth. This work therefore represents a significant step forward in the potential clinical translation of SERRS nanoparticles for high precision cancer imaging.

Khademi S., Sarkar S., Shakeri-Zadeh A., Attaran N., Kharrazi S., Ay M.R., Azimian H., Ghadiri H.

The development of various cost-effective multifunctional contrast agent for specific targeting molecular imaging of tumors presents a great challenge. We report here the in vivo targeting imaging of folic acid (FA) gold nanoparticles (AuNPs) through cysteamine (Cys) linking for targeted of human nasopharyngeal head and neck cancer by computed tomography (CT). The toxicity of nanoparticles in kidney, heart, spleen, brain and liver was evaluated by H&E (hematoxylin and eosin) assay. We showed that the formed FA-Cys-AuNPs with an Au core size of ˜13 nm are non-cytotoxic in the particle concentration of 3 × 103 μg/ ml. The nude mice were scanned using a 64-slice CT scan with parameters (80 kVp, slice thickness: 0.625 mm, mAs: 200, pitch: 1). CT scan was performed before and after (Three and six hours) I.V (Intra Venous) injection of AuNPs and FA-Cys-AuNPs. The distribution of nanoparticles in the nude mice was evaluated by imaging and coupled plasma optical emission spectrometry (ICP-OES) analysis. The findings clearly illustrated that a small tumor, which is undetectable via computed tomography, is enhanced by X-ray attenuation and becomes visible (4.30-times) by the molecularly targeted AuNPs. It was further demonstrated that active tumor cells targeting (FA-Cys-AuNPs) is more specific and efficient (2.03-times) than passive targeting AuNPs. According to the results, FA-Cys-AuNPs can be employed as a promising contrast agent in CT scan imaging and maybe in radiotherapy that require enhanced radiation dose.

Taverna C., Fasolato C., Brasili F., Ripanti F., Rizza C., De Marcellis A., Postorino P., Sennato S., Nucara A., Capocefalo A.

Mao J., Yan Y., Wu Q., Wang M., Dai J., Niu K., Zheng L., Jiang C., Jiang F., Zhang W., Tao K., Dai J.

Longhin E.M., Rios-Mondragon I., Mariussen E., Zheng C., Busquets M., Gajewicz-Skretna A., Hofshagen O., Bastus N.G., Puntes V.F., Cimpan M.R., Shaposhnikov S., Dusinska M., Rundén-Pran E.

Abstract Background Hazard and risk assessment of nanomaterials (NMs) face challenges due to, among others, the numerous existing nanoforms, discordant data and conflicting results found in the literature, and specific challenges in the application of strategies such as grouping and read-across, emphasizing the need for New Approach Methodologies (NAMs) to support Next Generation Risk Assessment (NGRA). Here these challenges are addressed in a study that couples physico-chemical characterization with in vitro investigations and in silico similarity analyses for nine nanoforms, having different chemical composition, sizes, aggregation states and shapes. For cytotoxicity assessment, three methods (Alamar Blue, Colony Forming Efficiency, and Electric Cell-Substrate Impedance Sensing) are applied in a cross-validation approach to support NAMs implementation into NGRA. Results The results highlight the role of physico-chemical properties in eliciting biological responses. Uptake studies reveal distinct cellular morphological changes. The cytotoxicity assessment shows varying responses among NMs, consistent among the three methods used, while only one nanoform gave a positive response in the genotoxicity assessment performed by comet assay. Conclusions The study highlights the potential of in silico models to effectively identify biologically active nanoforms based on their physico-chemical properties, reinforcing previous knowledge on the relevance of certain properties, such as aspect ratio. The potential of implementing in vitro methods into NGRA is underlined, cross-validating three cytotoxicity assessment methods, and showcasing their strength in terms of sensitivity and suitability for the testing of NMs. Graphical abstract Created with BioRender.com (publication license obtained)

Shi Z., Zhang Y., Xiao Y., Shi Z., Wei X., Wang B., Yuan Y., Li P.

Neurological disorders are characterized by high mortality and disability rates. Furthermore, the burden associated with disability and mortality resulting from neurological disorders has been increasing at an alarming rate. Botanical drugs and their bioactive components have emerged as a prominent area of research, offering a promising avenue for developing novel alternatives for treating neurological diseases. Gastrodin is the principal active component derived from the traditional Chinese medicinal plant Gastrodia elata Blume (GEB). Existing literature reveals that gastrodin exerts various pharmacological protective actions against neurological disorders. This review aimed to collate novel literature on gastrodin for treating neurological disorders from Web of Science, PubMed, Embase and CNKI. The pharmacokinetics of gastrodin, its therapeutic role in neurological disorders, the main mechanisms of action and clinical application were addressed. Furthermore, a detailed overview of gastrodin drug delivery systems and physical enhancement methods was presented, offering invaluable insights into potential research and the extensive applications of gastrodin.

Zaimoglu M., Secinti K.D., Altinoz M.A., Bozkurt M., Eroglu U., Ozpiskin O., Mammadkhanli O., Bayatli E., Caglar Y.S., Attar A.

Ramos-Pan L., Touzani A., Fernández-Bertólez N., Fraga S., Laffon B., Valdiglesias V.

Sarmin M., Gurung S., Sarkar S., Das S., Hoda M.

Trigonella foenum-graecum is an economically important plant that has significant nutraceutical properties. Various parts of the plant have previously been reported to synthesize metal nanoparticles. However, the seeds of the plant have limited potential to synthesize metal nanoparticles. Green synthesis of silver nanoparticles requires phytochemicals as reducing and metal chelating agents, in addition to the stabilizing agents that play critical role in nanoparticles stabilization. The quantitative analysis of the methanol extract of the seeds suggest that the extract has significant antioxidant activity and reducing potential which is comparable to that of ascorbic acid. Likewise, GCMS data of the extract identified several phytochemical components that have nanoparticles stabilizing potential. Evidently, the extract indeed synthesized silver nanoparticles in dark, albeit in very low quantity. This limitation of low quantity of nanoparticles synthesis was overcome by photocatalysis. The rate of nanoparticles synthesis increased significantly with increase in the intensity of the white light-emitting diode (LED) light. Furthermore, the photocatalytic effect of the white light also has significant impact on the physicochemical characterisation of the nanoparticles. Particle size, nanoparticles yield and elemental analysis demonstrated that the 2000 lumens white LED light is optimum for photocatalysis as compared to the 250 lumens and 825 lumens light. However, the stability of nanoparticles is not influenced by photoirradiation, and is rather controlled by the phytochemical composition of the extract. Methanol extract of the seeds significantly enhanced the stability of the silver nanoparticles irrespective of the light intensities used for photocatalysis.

Hlapisi N., Songca S.P., Ajibade P.A.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are potential cancer treatment methods that are minimally invasive with high specificity for malignant cells. Emerging research has concentrated on the application of metal nanoparticles encapsulated in porphyrin and their derivatives to improve the efficacy of these treatments. Gold and silver nanoparticles have distinct optical properties and biocompatibility, which makes them efficient materials for PDT and PTT. Conjugation of these nanoparticles with porphyrin derivatives increases their light absorption and singlet oxygen generation that create a synergistic effect that increases phototoxicity against cancer cells. Porphyrin encapsulation with gold or silver nanoparticles improves their solubility, stability, and targeted tumor delivery. This paper provides comprehensive review on the design, functionalization, and uses of plasmonic silver and gold nanoparticles in biomedicine and how they can be conjugated with porphyrins for synergistic therapeutic effects. Furthermore, it investigates this dual-modal therapy’s potential advantages and disadvantages and offers perspectives for future prospects. The possibility of developing gold, silver, and porphyrin nanotechnology-enabled biomedicine for combination therapy is also examined.

Nath S.G., Anila E.I.

In vivo bioimaging encompasses the non-invasive visualization of internal cells or organs within the human body, facilitating the real-time monitoring of dynamic biological processes. This form of bioimaging holds paramount significance within clinical domains due to its capacity to facilitate early disease detection, notably in cases of life-threatening conditions such as cancer. Although established imaging modalities like ultrasound, magnetic resonance imaging, and fluorescence imaging exist, the quest for innovative imaging probes with enhanced visibility to provide high-resolution images remains an active area of research. The introduction of persistent luminescent nanoprobes, characterized by their unique afterglow luminescence property, presents an exciting avenue in the realm of bioimaging. These nanoprobes offer several advantages over traditional fluorescent probes, notably in their ability to surmount light attenuation challenges within biological tissues including issues such as autofluorescence and light scattering. The chapter offers a succinct introduction to two pivotal facets of fluorescence imaging, namely persistent luminescence and upconversion luminescence while elucidating the underlying mechanisms governing their luminescence behavior. Moreover, this chapter provides comprehensive insights into various fluorescence imaging techniques, encompassing near-infrared imaging, upconversion imaging, X-ray-activated luminescence imaging, persistent luminescence imaging, and various multimodal imaging techniques.

Mgijima T., Sibuyi N.R., Fadaka A.O., Meyer S., Madiehe A.M., Meyer M., Onani M.O.

Huang H., Zheng Y., Chang M., Song J., Xia L., Wu C., Jia W., Ren H., Feng W., Chen Y.

Tapia-Arellano A., Cabrera P., Cortés-Adasme E., Riveros A., Hassan N., Kogan M.J.

AbstractThe use of nanomaterials in medicine offers multiple opportunities to address neurodegenerative disorders such as Alzheimer's and Parkinson's disease. These diseases are a significant burden for society and the health system, affecting millions of people worldwide without sensitive and selective diagnostic methodologies or effective treatments to stop their progression. In this sense, the use of gold nanoparticles is a promising tool due to their unique properties at the nanometric level. They can be functionalized with specific molecules to selectively target pathological proteins such as Tau and α-synuclein for Alzheimer’s and Parkinson’s disease, respectively. Additionally, these proteins are used as diagnostic biomarkers, wherein gold nanoparticles play a key role in enhancing their signal, even at the low concentrations present in biological samples such as blood or cerebrospinal fluid, thus enabling an early and accurate diagnosis. On the other hand, gold nanoparticles act as drug delivery platforms, bringing therapeutic agents directly into the brain, improving treatment efficiency and precision, and reducing side effects in healthy tissues. However, despite the exciting potential of gold nanoparticles, it is crucial to address the challenges and issues associated with their use in the medical field before they can be widely applied in clinical settings. It is critical to ensure the safety and biocompatibility of these nanomaterials in the context of the central nervous system. Therefore, rigorous preclinical and clinical studies are needed to assess the efficacy and feasibility of these strategies in patients. Since there is scarce and sometimes contradictory literature about their use in this context, the main aim of this review is to discuss and analyze the current state-of-the-art of gold nanoparticles in relation to delivery, diagnosis, and therapy for Alzheimer’s and Parkinson’s disease, as well as recent research about their use in preclinical, clinical, and emerging research areas. Graphical Abstract

Zodape S.J., Barai D.P., Bhanvase B.A.

Lei T., Yang Z., Li H., Qin M., Gao H.

Emerging evidence suggests that vascular pathological changes play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The dysfunction of the cerebral vasculature occurs in the early course of AD, characterized by alterations in vascular morphology, diminished cerebral blood flow (CBF), impairment of the neurovascular unit (NVU), vasculature inflammation, and cerebral amyloid angiopathy. Vascular dysfunction not only facilitates the influx of neurotoxic substances into the brain, triggering inflammation and immune responses but also hampers the efflux of toxic proteins such as Aβ from the brain, thereby contributing to neurodegenerative changes in AD. Furthermore, these vascular changes significantly impact drug delivery and distribution within the brain. Therefore, developing targeted delivery systems or therapeutic strategies based on vascular alterations may potentially represent a novel breakthrough in AD treatment. This review comprehensively examines various aspects of vascular alterations in AD and outlines the current interactions between nanoparticles and pathological changes of vascular.

Massironi A.

Abstract: Hybrid functional materials, composed of inorganic and organic components, are considered versatile platforms whose applications in electronics, optics, mechanics, energy storage, informatics, catalysis, sensors, and medicine field have represented a breakthrough for human well-being. Among hybrid materials, micro/nanostructured hybrid colloidal systems have been widely investigated due to the dramatic enhancement of activity provided by the large surface area exposed at the interfaces with respect to the bulk counterpart. Recently, a growing interest has been in the exploration of novel environmental-friendly and versatile procedures that allow the formulation of hybrid nanostructures through safety procedures and mild experimental conditions. This review aims to provide an introduction to hybrid organic-inorganic materials for biomedical applications in particular nanostructured ones, describing the commonly exploited materials for their fabrication and techniques, advantages, and drawbacks.