Multifunctional nanomaterials for smart wearable diabetic healthcare devices.

Wearable diabetic healthcare devices have attracted great attention for real-time continuous glucose monitoring (CGM) using biofluids such as tears, sweat, saliva, and interstitial fluid via noninvasive ways. In response to the escalating global demand for CGM, these devices enable proactive management and intervention of diabetic patients with incorporated drug delivery systems (DDSs). In this context, multifunctional nanomaterials can trigger the development of innovative sensing and management platforms to facilitate real-time selective glucose monitoring with remarkable sensitivity, on-demand drug delivery, and wireless power and data transmission. The seamless integration into wearable devices ensures patient's compliance. This comprehensive review evaluates the multifaceted roles of these materials in wearable diabetic healthcare devices, comparing their glucose sensing capabilities with conventionally available glucometers and CGM devices, and finally outlines the merits, limitations, and prospects of these devices. This review would serve as a valuable resource, elucidating the intricate functions of nanomaterials for the successful development of advanced wearable devices in diabetes management.

Emerging strategies to fabricate polymeric nanocarriers for enhanced drug delivery across blood-brain barrier: An overview.

Blood-brain barrier (BBB) serves as an essential interface between central nervous system (CNS) and its periphery, allowing selective permeation of ions, gaseous molecules, and other nutrients to maintain metabolic functions of brain. Concurrently, it restricts passage of unsolicited materials from bloodstream to CNS which could otherwise lead to neurotoxicity. Nevertheless, in the treatment of neurodegenerative diseases such as Parkinson's, Alzheimer's, diffuse intrinsic pontine glioma, and other brain cancers, drugs must reach CNS. Among various materials developed for this purpose, a few judiciously selected polymeric nanocarriers are reported to be highly prospective to facilitate BBB permeation. However, the challenge of transporting drug-loaded nanomaterials across this barrier remains formidable. Herein a concise analysis of recently employed strategies for designing polymeric nanocarriers to deliver therapeutics across BBB is presented. Impacts of 3Ss, namely, size, shape, and surface charge of polymeric nanocarriers on BBB permeation along with different ligands used for nanoparticle surface modification to achieve targeted delivery have been scrutinized. Finally, we elucidated future research directions in the context of designing smart polymeric nanocarriers for BBB permeation. This work aims to guide researchers engaged in polymeric nanocarrier design, helping them navigate where to begin, what challenges to address, and how to proceed effectively.

Microwave-assisted rapid synthesis of nitrogen-enriched amphibious carbon quantum dots for sensitive detection of ROS and multiple other applications.

Carbon quantum dots (CQDs) have gained tremendous attention due to their pertinence in diverse application fields. Herein, we report the application of nitrogen-doped CQDs (N-CQDs) for the sensitive detection of reactive oxygen species (ROS) in vitro. The N-CQDs were synthesized via a rapid, one-pot, cost-effective and environmentally friendly approach, and exhibited amphibious solubility in solvents with a wide range of relative polarities from 1 to 0.4. Spectroscopic and microscopic techniques were used to accomplish the functional, morphological, and optical characterization of these nanoparticles. The as-synthesized luminous N-CQDs reproducibly demonstrated an average size distribution with a diameter of 5-6 nm. Their suitability for multiple other applications, such as metal sensing, confidential information inscription, hosting on cellulose materials with long-standing stability, designing polysaccharide molds flashing bright fluorescence, fingerprint imprinting, and in vitro bioimaging has also been exhibited. The plausible mechanism of peroxide induced fluorescence quenching of CQDs is presented. Treatment of human neuroblastoma cells SH-SY5Y with 1000 µg mL-1 N-CQDs demonstrated excellent (∼100%) cell viability. An empirical relation between fluorescent intensity of N-CQDs as a function of the concentration of oxidants inside single-cells has been established for the first time.

Influence of Molecular Structures on Fluorescence of Flavonoids and Their Detection in Mammalian Cells.

Flavonoids are being increasingly applied for the treatment of various diseases due to their anti-cancer, anti-oxidant, anti-inflammatory, and anti-viral properties. However, it is often challenging to detect their presence in cells and tissues through bioimaging, as most of them are not fluorescent or are too weak to visualize. Here, fluorescence possibilities of nine naturally occurring analogous flavonoids have been investigated through UV/visible spectroscopy, molecular structure examination, fluorescent images in mammalian cells and their statistical analysis employing aluminum chloride and diphenylboric acid 2-aminoethyl ester as fluorescence enhancers. It is found that, in order to form a stable fluorescent complex with an enhancer, flavonoids should have a keto group at C4 position and at least one -OH group at C3 or C5 position. Additionally, the presence of a double bond at C2-C3 can stabilize extended quinonoid structure at the cinnamoyl moiety, which thereby enhances the complex stability. A possible restriction to the free rotation of ring B around C1'-C2 single bond can contribute to the further enhancement of fluorescence. Thus, these findings can act as a guide for distinguishing flavonoids capable of exhibiting fluorescence from thousands of their analogues. Finally, using this technique, flavonoids are detected in neuroblastoma cells and their time course assay is conducted via fluorescence imaging. Their cellular uptake efficiency is found to be high and differential in nature and their distribution throughout the cytoplasm is clearly detected.

pH-responsive polyelectrolyte complexation on upconversion nanoparticles: a multifunctional nanocarrier for protection, delivery, and 3D-imaging of therapeutic protein.

The delicate tertiary structure of proteins, their susceptibility to heat- and enzyme-induced irreversible denaturation, and their tendency to get accumulated at the cell membrane during uptake are daunting challenges in proteinaceous therapeutic delivery. Herein, a polyelectrolyte complex having encapsulated therapeutic protein has been designed on the surface of upconverting luminescent nanoparticles (NaYF4:20%Yb3+,2%Er3+). This nanosized complex system has been found to overcome the challenges of protein aggregation at the cell membrane. It has also defended the cargo from denaturation against (a) enzymatic action of proteinase K and (b) heat (up to 60 °C). Additionally, the nanoparticles at the core of the loaded carrier served as near-infrared (980 nm) responsive probe to accomplish extended-duration 3D imaging during protein delivery. The outer layer of polymer played pivotal role to protect/retrieve the protein structure from denaturation as investigated by circular dichroism studies. Both the masked surface-charges of protein and the nanoscale size of the loaded carrier have facilitated their efficient passage through the cell membrane as observed through 3D images/videos. This nanocarrier is the first of its kind for direct delivery of protein. Thus, the findings can be useful to protect and transport various proteinaceous materials to overcome challenges of accumulation at the cell-membrane and low-temperature storage, as nature does.

Structure-Based Varieties of Polymeric Nanocarriers and Influences of Their Physicochemical Properties on Drug Delivery Profiles.

Carriers are equally important as drugs. They can substantially improve bioavailability of cargos and safeguard healthy cells from toxic effects of certain therapeutics. Recently, polymeric nanocarriers (PNCs) have achieved significant success in delivering drugs not only to cells but also to subcellular organelles. Variety of natural sources, availability of different synthetic routes, versatile molecular architectures, exploitable physicochemical properties, biocompatibility, and biodegradability have presented polymers as one of the most desired materials for nanocarrier design. Recent innovative concepts and advances in PNC-associated nanotechnology are providing unprecedented opportunities to engineer nanocarriers and their functions. The efficiency of therapeutic loading has got considerably increased. Structural design-based varieties of PNCs are widely employed for the delivery of small therapeutic molecules to genes, and proteins. PNCs have gained ever-increasing attention and certainly paves the way to develop advanced nanomedicines. This article presents a comprehensive investigation of structural design-based varieties of PNCs and the influences of their physicochemical properties on drug delivery profiles with perspectives highlighting the inevitability of incorporating both the multi-stimuli-responsive and multi-drug delivery properties in a single carrier to design intelligent PNCs as new and emerging research directions in this rapidly developing area.

Polyelectrolyte-Dye Interactions: An Overview.

Polyelectrolytes are polymers with repeating units of ionizable groups coupled with counterions. Recently, polyelectrolytes have drawn significant attention as highly promising macromolecular materials with potential for applications in almost every sector of our daily lives. Dyes are another class of chemical compounds that can interact with substrates and subsequently impart color through the selective absorption of electromagnetic radiation in the visible range. This overview begins with an introduction to polyelectrolytes and dyes with their respective definitions, classifications (based on origin, molecular architecture, etc.), and applications in diverse fields. Thereafter, it explores the different possible interactions between polyelectrolytes and dyes, which is the main focus of this study. The various mechanisms involved in dye-polyelectrolyte interactions and the factors that influence them are also surveyed. Finally, these discussions are summarized, and their future perspectives are presented.

Hydrodynamic and conformational characterization of aqueous sodium alginate solutions with varying salinity.

Insight into the role of electrostatic interactions on the hydrodynamics and conformation of aqueous sodium alginate was gained through viscometry. Alginate chains are found to shrink in salt-free solutions more rapidly with increasing polymer concentration compared to salt-solutions. For salt-free solutions, a reduced polymer concentration of less than 1 suffices to make the alginate coil volume half of that at infinite dilution which becomes invariant when the reduced concentration exceeds 8. In saline media having salt concentration greater than 0.1 mol·L-1, the chains become more flexible, caused by the shielding of intra-chain repulsions. The chains effectively reached unperturbed state when the added salt concentration becomes ≥0.5 mol·L-1. Alginate chains are shown to remain stiff up to about 8-10 monomers within the investigated temperature range. This study explores the possible modification of the individual chain behavior induced by the neighboring chains or by the variation of temperature.

Isoprocurcumenol Supports Keratinocyte Growth and Survival through Epidermal Growth Factor Receptor Activation.

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried to utilize epidermal growth factor (EGF), but achieved limited success. Therefore, a small natural compound that can mimic the activity of EGF is highly desired in both medical and cosmetic fields. Here, using the modified biosensor system, we observed that natural small-compound isoprocurcumenol, which is a terpenoid molecule derived from turmeric, can activate EGFR signaling. It increased the phosphorylation of ERK and AKT, and upregulated the expression of genes related to cell growth and proliferation, such as c-myc, c-jun, c-fos, and egr-1. In addition, isoprocurcumenol induced the proliferation of keratinocytes in both physical and UVB-induced cellular damage, indicative of its function in skin regeneration. These findings reveal that EGF-like isoprocurcumenol promotes the proliferation of keratinocytes and further suggest its potential as an ingredient for medical and cosmetics use.

Near-Infrared-Triggered Upconverting Nanoparticles for Biomedicine Applications.

Due to the unique properties of lanthanide-doped upconverting nanoparticles (UCNP) under near-infrared (NIR) light, the last decade has shown a sharp progress in their biomedicine applications. Advances in the techniques for polymer, dye, and bio-molecule conjugation on the surface of the nanoparticles has further expanded their dynamic opportunities for optogenetics, oncotherapy and bioimaging. In this account, considering the primary benefits such as the absence of photobleaching, photoblinking, and autofluorescence of UCNPs not only facilitate the construction of accurate, sensitive and multifunctional nanoprobes, but also improve therapeutic and diagnostic results. We introduce, with the basic knowledge of upconversion, unique properties of UCNPs and the mechanisms involved in photon upconversion and discuss how UCNPs can be implemented in biological practices. In this focused review, we categorize the applications of UCNP-based various strategies into the following domains: neuromodulation, immunotherapy, drug delivery, photodynamic and photothermal therapy, bioimaging and biosensing. Herein, we also discuss the current emerging bioapplications with cutting edge nano-/biointerfacing of UCNPs. Finally, this review provides concluding remarks on future opportunities and challenges on clinical translation of UCNPs-based nanotechnology research.

Uptake of Polyelectrolyte Functionalized Upconversion Nanoparticles by Tau-Aggregated Neuron Cells.

Tauopathy is the aggregation phenomenon of tau proteins and associated with neurodegenerative diseases. It metastasizes via the transfer of tau aggregates to adjacent neuron cells; however, the mechanism has not yet been fully understood. Moreover, if the materials used for designing drug delivery system to treat such neurodegenerative diseases do not undergo biodegradation or exocytosis but remains in cells or tissues, they raise concerns about their possible negative impacts. In this study, the uptake and delivery mechanisms of nano-sized carriers in tau aggregated neuron cells were investigated employing polyelectrolyte-functionalized upconversion nanoparticles (UCNPs) of diameter ~100 nm. Investigation through bioimaging was carried out by irradiating the particles with near-infrared light. Here, forskolin and okadaic acid were employed to induce tau aggregation into healthy neuron cells. It was noticed that the tau-aggregated neuron cells, when treated with relatively large sized UCNPs, showed uptake efficiency similar to that of normal neuron cells however their intracellular transport and exocytosis were impacted, and most of the carriers remained accumulated around lysosome. This demonstrates that metastasis mechanisms of tauopathy can get influenced by the size of carriers and are to be considered during their pharmacokinetic studies which is often not addressed in many drug delivery studies.

Designing Microparticle-Impregnated Polyelectrolyte Composite: The Combination of ATRP, Fast Azidation, and Click Reaction Using a Single-Catalyst, Single-Pot Strategy.

Polystyrene microparticles were covalently impregnated into the networks of functional polyelectrolyte chains designed via a tandem run of three reactions: (i) synthesis of water-soluble polyelectrolyte, (ii) fast azidation and (iii) a 'click' reaction, using the single-catalyst, single-pot strategy at room temperature in mild aqueous media. The model polyelectrolyte sodium polystyrenesulfonate (NaPSS) was synthesized via the well-controlled atom transfer radical polymerization (ATRP) whose halogen living-end was transformed to azide and subsequently coupled with an alkyne carboxylic acid through a 'click' reaction using the same ATRP catalyst, throughout. Halogen to azide transformation was fast and followed the radical pathway, which was explained through a plausible mechanism. Finally, the success of microparticle impregnation into the NaPSS network was evaluated through Kaiser assay and imaging. This versatile synthetic procedure, having a reduced number of discrete reaction steps and eliminated intermediate work-ups, has established a fast and simple pathway to design functional polymers required to fabricate stable polymer-particle composites where the particles are impregnated covalently and controllably.

Recent progress on biocompatible nanocarrier-based genistein delivery systems in cancer therapy.

Diets with naturally occuring chemopreventive agents are showing good potentials in serving dual purposes: firstly, for maintaining health, and secondly, for emerging as most puissant cost-effective strategy against chronic diseases like cancer. Genistein, one of the active soy isoflavone, is gaining attention due to its ability to impede carcinogenic processes by regulating wide range of associated molecules and signalling mechanisms. Epidemiologic and preclinical evidences suggest that sufficient consumption of soy-based food having genistein can be correlated to the reduction of cancer risk. However, certain adverse effects like poor oral bioavailability, low aqueous solubility and inefficient pharmacokinetics have pushed it down in the list of phytoconstituents currently undergoing successful clinical trials. In order to maximise the utilisation of therapeutic benefits of this phytoestrogen, suitable drug carrier designs are required. Recently, nanocarriers, mainly composed of polymeric materials, are progressively and innovatively exploited with the aim to improve pharmacokinetics and pharmacodynamics of genistein. Here, we have briefly reviewed (a) the targeted molecular mechanisms of geinstein, (b) nanopolymeric approaches opted so far in designing carriers and (c) the reasons behind their restricted clinical applications. Finally, some mechanism-based approaches are proposed presenting genistein as the future paradigm in cancer therapy.

Cancer therapeutics with epigallocatechin-3-gallate encapsulated in biopolymeric nanoparticles.

With the recent quantum leap in chemoprevention by dietary products, their use as cancer therapeutics is garnering worldwide attention. The concept of effortlessly fighting this deadly disease by gulping cups of green tea or swallowing green tea extract capsules is appreciated universally. Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, has generated significant interest in controlling carcinogenesis due to its growth-inhibitory efficacy against a variety of cancers by targeting multiple signaling pathways. However, the success of EGCG in preclinical studies is difficult to translate into clinical trials due to issues of low solubility, bioavailability and an uncertain therapeutic window. The laborious and expensive journey of drugs from the laboratory to commercialization can be improved by utilizing nanoparticles as anti-cancer drug carriers. Exploitation of biopolymeric nanoparticles in recent years has improved EGCG's biodistribution, stability and tumor selectivity, revealing its superior chemopreventive effects. This review briefly summarizes recent developments regarding the targets and side effects of EGCG, complications associated with its low bioavailability and critically analyses the application of biopolymeric nanoparticles encapsulating EGCG as a next generation delivery systems.

Long-Standing Stability of Silver Nanorod Array Substrates Functionalized Using a Series of Thiols for a SERS-Based Sensing Application.

Silver nanorod (AgNR) array substrates were fabricated using an oblique angle thermal evaporation technique; their long-term stability, surface uniformity and reproducibility, which are primary requirements for their widespread realistic application and commercialization, were assessed using surface-enhanced Raman scattering (SERS) spectroscopy. The nanorod surfaces were functionalized using a series of organic thiols, which range from hydrophilic to hydrophobic, to mimic various conditions that often arise during detection of hydrophilic/phobic analytes in a realistic application field. A group of these functionalized substrates was stored in ambient laboratory atmosphere; another in light minimized, moisture-free vacuum; while another was stowed carefully and neatly in water to mimic realistic conditions. The effects of these storing conditions were studied. A surfactant was added to the water to maintain consistent surface wetting in the third group. SERS spectra of nanorod substrates prior to functionalization were also recorded to investigate the effect of adventitious carbonaceous contaminants. A meticulous systematic study on the reproducibility of SERS signals was carried out: spot-to-spot, substrate-to-substrate, batch-to-batch, day-to-day. The relative standard deviation (RSD) shown by the SERS signals acquired from various spots of a single substrate was less than 3%, which is very similar to the only account reported so far, in which RSD is reported as 2%. The wetting behavior of these thiol functionalized AgNR substrates are investigated using static contact angle measurements. The functionalized substrates have exhibited excellent long-standing stability over a period of six months when stored appropriately; hence, they are highly suitable for mass production towards realistic application.

Morphological and SERS Properties of Silver Nanorod Array Films Fabricated by Oblique Thermal Evaporation at Various Substrate Temperatures.

Aligned silver nanorod (AgNR) array films were fabricated by oblique thermal evaporation. The substrate temperature during evaporation was varied from 10 to 100 °C using a home-built water cooling system. Deposition angle and substrate temperature were found to be the most important parameters for the morphology of fabricated films. Especially, it was found that there exists a critical temperature at ~90 °C for the formation of the AgNR array. The highest enhancement factor of the surface-enhanced Raman scattering (SERS), observed in the Ag films coated with benzenethiol monolayer, was ~6 × 10(7). Hot spots, excited in narrow gaps between nanorods, were attributed to the huge enhancement factor by our finite-difference time-domain (FDTD) simulation reflecting the real morphology.

Sodium carboxymethylcellulose-induced aggregation of 1-decyl-3-methylimidazolium chloride in aqueous solutions.

Aggregation behavior of a surface active ionic liquid 1-decyl-3-methylimidazolium chloride (C10MeImCl) was studied in aqueous solutions in absence and in presence of sodium carboxymethylcellulose (NaCMC) by electrical conductivity, surface tension, vapor pressure, and fluorescence measurements. Ion-association behavior of C10MeImCl (aq) in the premicellar regime has also been investigated. Two characteristic concentrations, namely the critical aggregation concentration and polymer saturation concentration, before free C10MeImCl micelles appear in C10MeImCl-NaCMC solutions were identified. Effects of temperature, NaCMC concentration, and the bulk solution structural property on the self-aggregation of C10MeImCl have been discussed to elucidate C10MeImCl-NaCMC interactions. Thermodynamics of the micellization processes provided important insight regarding the (a) release of water molecules from the hydration layer around the hydrophilic domain, and from the water cage around the hydrophobic moiety of the SAIL, and (b) transfer of the hydrocarbon chains into the micelle and restoration of the H-bonding structure of the water around the micelle.

Influence of sodium carboxymethylcellulose on the aggregation behavior of aqueous 1-hexadecyl-3-methylimidazolium chloride solutions.

The influence of sodium carboxymethylcellulose (NaCMC) on the aggregation phenomena of a surface active ionic liquid 1-hexadecyl-3-methylimidazolium chloride (C16MeImCl) was studied in aqueous solutions using electrical conductivity and surface tension measurements. The counterion condensation behavior of NaCMC (aq) and the premicellar ion-association behavior of C16MeImCl (aq) were also investigated. Two characteristic concentrations, namely the critical aggregation concentration and polymer saturation concentration, before free C16MeImCl micelles appear in C16MeImCl-NaCMC solutions have been identified. Effects of temperature, NaCMC concentration, and the charge density parameter of NaCMC on the self-aggregation of the C16MeImCl have been discussed to elucidate C16MeImCl-NaCMC interactions. The thermodynamic parameters for micellization of C16MeImCl were estimated both in absence and in the presence of NaCMC. The observed enthalpy-entropy compensation effect in C16MeImCl and C16MeImCl-NaCMC systems provided important insight as to how micellization processes are governed by the bulk structural property of the solution with respect to that of the water.