Platinum Nanozyme-Enabled Colorimetric Determination of Total Antioxidant Level in Saliva.

Redox imbalance and oxidative stress-related biomarkers are raising increasing consensus in the scientific community for their significant role in a wide range of human disorders. In this framework, the total antioxidant capacity (TAC), namely, the overall pattern of both enzymatic and nonenzymatic antioxidant compounds within the body, represents an important bioanalytical parameter. To date, however, antioxidant assays require costly instrumentations, laboratory setups, and reagents, and they are invasive. Yet, their accuracy typically suffers from strong sensitivity to interfering matrices and inability to detect the complete pattern of physiological antioxidant molecules, due to the use of reaction schemes and probes/substrates that are not sensitive to the diverse range of relevant target species. Here, we exploit the enzyme-mimetic properties of platinum nanoparticles combined with hydroxyl radical probes produced at the particle surface to develop an effective detection scheme that is sensitive to both single electron transfer (SET) and hydrogen atom transfer (HAT) reactions, thus covering all the physiologically relevant antioxidant species. Importantly, the nanozyme-enabled method allows fast (5 min), accurate, and noninvasive evaluation of the body TAC through saliva via simple naked-eye or smartphone-based inspection.

Platinum nanoparticles in nanobiomedicine.

Oxidative stress-dependent inflammatory diseases represent a major concern for the population's health worldwide. Biocompatible nanomaterials with enzymatic properties could play a crucial role in the treatment of such pathologies. In this respect, platinum nanoparticles (PtNPs) are promising candidates, showing remarkable catalytic activity, able to reduce the intracellular reactive oxygen species (ROS) levels and impair the downstream pathways leading to inflammation. This review reports a critical overview of the growing evidence revealing the anti-inflammatory ability of PtNPs and their potential applications in nanomedicine. It provides a detailed description of the wide variety of synthetic methods recently developed, with particular attention to the aspects influencing biocompatibility. Special attention has been paid to the studies describing the toxicological profile of PtNPs with an attempt to draw critical conclusions. The emerging picture suggests that the material per se is not causing cytotoxicity, while other physicochemical features related to the synthesis and surface functionalization may play a crucial role in determining the observed impairment of cellular functions. The enzymatic activity of PtNPs is also summarized, analyzing their action against ROS produced by pathological conditions within the cells. In particular, we extensively discuss the potential of these properties in nanomedicine to down-regulate inflammatory pathways or to be employed as diagnostic tools with colorimetric readout. A brief overview of other biomedical applications of nanoplatinum is also presented.

A dual-color plasmonic immunosensor for salivary cortisol measurement.

Lifestyle-related disorders are a public health problem worldwide and their early diagnosis represents the key to successful therapies. In this framework, rapid point-of-care (POC) tests are one of the most promising diagnostic techniques. In particular, the use of saliva is raising increasing interest as a noninvasive biological fluid in POC systems, although the low concentration of salivary biomarkers typically requires strong advances to improve the device sensitivity. In this study, the plasmonic properties of two differently shaped gold nanoparticles (i.e., nanospheres and nanostars) were combined to develop an efficient paper-based immunosensor for the naked-eye evaluation of salivary cortisol, known as one of the main stress-related biomarkers. Notably, the dual-color system facilitated an immediate and easy evaluation of cortisol levels, based on a blue-to-pink color change of the detection zone. Furthermore, the implemented strategy showed potential applicability as a rapid and portable monitoring system, allowing discriminating different target concentrations.

A multi-line platinum nanozyme-based lateral flow device for the colorimetric evaluation of total antioxidant capacity in different matrices.

The evaluation of Total Antioxidant Capacity (TAC), namely the complete pattern of antioxidant species in a complex medium, is of major interest in many fields ranging from health monitoring to quality control in the food industry. In this framework, point-of-care (POC) testing technologies are a promising diagnostic solution for rapid on-site analyses, unlike laboratory based-assays, which are often limited by centralized analyses, time-consuming and costly procedures, and invasiveness in the case of health diagnostics. In this work, we developed a POC methodology that evaluates TAC in different matrices, exploiting the peroxidase-like properties of 5 nm platinum nanoparticles (PtNPs), combined with a colorimetric paper-based device. Notably, we designed and optimized a multi-line PtNPs-based Lateral Flow Assay (LFA), which relies on three sequential test lines with increasing concentrations of platinum nanozymes, to get a non-invasive, accurate, and fast (10 minutes) colorimetric evaluation of the body TAC in saliva samples. Furthermore, we employed the device as a prototype of a quality control tool in the food industry, for the determination of the TAC in fruit juices.

Nanocatalyst-Enabled Physically Unclonable Functions as Smart Anticounterfeiting Tags with AI-Aided Smartphone Authentication.

Counterfeiting is a worldwide issue affecting many industrial sectors, ranging from specialized technologies to retail market, such as fashion brands, pharmaceutical products, and consumer electronics. Counterfeiting is not only a huge economic burden (>$ 1 trillion losses/year), but it also represents a serious risk to human health, for example, due to the exponential increase of fake drugs and food products invading the market. Considering such a global problem, numerous anticounterfeit technologies have been recently proposed, mostly based on tags. The most advanced category, based on encryption and cryptography, is represented by physically unclonable functions (PUFs). A PUF tag is based on a unique physical object generated through chemical methods with virtually endless possible combinations, providing remarkable encoding capability. However, most methods adopted nowadays are based on expensive and complex technologies, relying on instrumental readouts, which make them not effective in real-world applications. To achieve a simple yet cryptography-based anticounterfeit method, herein we exploit a combination of nanotechnology, chemistry, and artificial intelligence (AI). Notably, we developed platinum nanocatalyst-enabled visual tags, exhibiting the properties of PUFs (encoding capability >10300) along with fast (1 min) ON/OFF readout and full reversibility, enabling multiple onsite authentication cycles. The development of an accurate AI-aided algorithm powers the system, allowing for smartphone-based PUF authentications.

Intracellular Antioxidant Activity of Biocompatible Citrate-Capped Palladium Nanozymes.

A method for the aqueous synthesis of stable and biocompatible citrate-coated palladium nanoparticles (PdNPs) in the size range comparable to natural enzymes (4-8 nm) has been developed. The toxicological profile of PdNPs was assessed by different assays on several cell lines demonstrating their safety in vitro also at high particle concentrations. To elucidate their cellular fate upon uptake, the localization of PdNPs was analyzed by Transmission Electron Microscopy (TEM). Moreover, crucial information about their intracellular stability and oxidation state was obtained by Sputtering-Enabled Intracellular X-ray Photoelectron Spectroscopy (SEI-XPS). TEM/XPS results showed significant stability of PdNPs in the cellular environment, an important feature for their biocompatibility and potential for biomedical applications. On the catalytic side, these PdNPs exhibited strong and broad antioxidant activities, being able to mimic the three main antioxidant cellular enzymes, i.e., peroxidase, catalase, and superoxide dismutase. Remarkably, using an experimental model of a human oxidative stress-related disease, we demonstrated the effectiveness of PdNPs as antioxidant nanozymes within the cellular environment, showing that they are able to completely re-establish the physiological Reactive Oxygen Species (ROS) levels in highly compromised intracellular redox conditions.

Multifunctional Platinum@BSA-Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation.

Platinum nanoparticles (PtNPs) are antioxidant enzyme-mimetic nanomaterials with significant potential for the treatment of complex diseases related to oxidative stress. Among such diseases, Cerebral Cavernous Malformation (CCM) is a major cerebrovascular disorder of genetic origin, which affects at least 0.5% of the general population. Accumulated evidence indicates that loss-of-function mutations of the three known CCM genes predispose endothelial cells to oxidative stress-mediated dysfunctions by affecting distinct redox-sensitive signaling pathways and mechanisms, including pro-oxidant and antioxidant pathways and autophagy. A multitargeted combinatorial therapy might thereby represent a promising strategy for the effective treatment of this disease. Herein, we developed a multifunctional nanocarrier by combining the radical scavenging activity of PtNPs with the autophagy-stimulating activity of rapamycin (Rapa). Our results show that the combinatorial targeting of redox signaling and autophagy dysfunctions is effective in rescuing major molecular and cellular hallmarks of CCM disease, suggesting its potential for the treatment of this and other oxidative stress-related diseases.

Citrate-Coated, Size-Tunable Octahedral Platinum Nanocrystals: A Novel Route for Advanced Electrocatalysts.

The development of green and scalable syntheses for the preparation of size- and shape-controlled metal nanocrystals is of high interest in many areas, including catalysis, electrocatalysis, nanomedicine, and electronics. In this work, a new synthetic approach based on the synergistic action of physical parameters and reagents produces size-tunable octahedral Pt nanocrystals, without the use of catalyst-poisoning reagents and/or difficult-to-remove coatings. The synthesis requires sodium citrate, ascorbic acid, and fine control of the reduction rate in aqueous environment. Pt octahedral nanocrystals with particle size as low as 7 nm and highly developed {111} facets have been achieved, as demonstrated by transmission electron microscopy, X-ray diffraction, and electrochemical methods. The absence of sticky molecules together with the high quality of the surface makes these nanocrystals ideal candidates in electrocatalysis. Notably, 7 nm bismuth-decorated octahedral nanocrystals exhibit superior performance for the electrooxidation of formic acid in terms of both specific and mass activities.

Assessment of collagen crosslinking and denaturation for the design of regenerative scaffolds.

Crosslinking and denaturation were two variables that deeply affected the performance of collagen-based scaffolds designed for tissue regeneration. If crosslinking enhances the mechanical properties and the enzymatic resistance of collagen, while masking or reducing the available cell binding sites, denaturation has very opposite effects, as it impairs the mechanical and the enzymatic stability of collagen, but increases the number of exposed cell adhesive domains. The quantification of both crosslinking and denaturation was thus fundamental to the design of collagen-based scaffolds for selected applications. The aim of this work was to investigate the extents of crosslinking and denaturation of collagen-based films upon dehydrothermal (DHT) treatment, that is, one of the most commonly employed methods for zero-length crosslinking that shows the unique ability to induce partial denaturation. Swelling measurements, differential scanning calorimetry, Fourier transform infrared spectroscopy, colorimetric assays for the quantification of primary amines, and mechanical tests were performed to analyze the effect of the DHT temperature on crosslinking and denaturation. In particular, chemically effective and elastically effective crosslink densities were evaluated. Both crosslinking and denaturation were found to increase with the DHT temperature, although according to different trends. The results also showed that DHT treatments performed at temperatures up to 120°C maintained the extent of denaturation under 25%. Coupling a mild DHT treatment with further crosslinking may thus be very useful not only to modulate the crosslink density, but also to induce a limited amount of denaturation, which shows potential to partially compensate the loss of cell binding sites caused by crosslinking.

Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model.

In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.