Nanoscale Systems Research Articles

Size and Surface Effects in the Ultrafast Dynamics of Strongly Cooperative Spin‐Crossover Nanoparticles

AbstractCooperative photoinduced switching of molecular materials at the nanoscale is still in its infancy. Strongly cooperative spin‐crossover nanomaterials are arguably the best prototypes of photomagnetic and volume‐changing materials that can be manipulated by short pulses of light. Open questions remain regarding their non‐equilibrium dynamics upon light excitation and the role of cooperative elastic interactions in nanoscale systems that are characterized by large surface/volume ratios. Femtosecond‐resolved broadband spectroscopy is performed on nanorods of the strongly cooperative Fe‐triazole, which undergoes a reversible low‐spin to high‐spin (HS) phase transition ≈360 K. Supported by density functional theory and mechano‐elastic Monte Carlo simulations, a marked difference is observed in the photoswitching dynamics at the surface of the nanoparticles compared with the core. Surprisingly, under low excitation (<2%) conditions, there occurs a transient increase in the HS population at the surface on the picosecond time scale, while the HS population in the core decays concomitantly. These results shed light onto the importance of surface properties and dynamical size limits of nanoscale photoresponsive nanomaterials that can be used in a broad range of applications.

Hyaluronic acid-functionalized MOFs for combined sunitinib and siRNA therapy in renal cell carcinoma

Sunitinib is a first-line treatment for renal cell carcinoma (RCC), but suffers from drug resistance, causing therapy failure. Therefore, nano-scale delivery systems should be introduced for targeted delivery. Metal-organic frameworks (MOFs) are attractive drug carriers that not only enable multidrug combination therapies but also exert photodynamic effects by incorporating photosensitizers as components. Here, a Zr-based porphyrinic nanoscale MOF, PCN224, was prepared as the carrier for the co-delivery of sunitinib and the siRNA against vascular endothelial growth factor receptor-2 (VEGFR-2). Drug-loaded PCN-224 is coated with hyaluronic acid (HA) to prevent drug molecular leakage and to exert tumor-targeting effects (CD44 in tumor cells). Photodynamic therapy was conducted under 660 nm laser (50 mW·cm−2, 10 min) irradiation. Compared with St/siVEGFR-2@PCN-224@HA without the HA coating, St/siVEGFR-2@PCN-224@HA significantly suppressed cell viability and promoted cell apoptosis. Laser irradiation further increased the anti-cancer effect of St/siVEGFR-2@PCN-224@HA by generating cytotoxic ROS. H&E staining of major organs revealed no signs of damage, indicating the biosafety of St/siVEGFR-2@PCN-224@HA. The prepared St/siVEGFR-2@PCN-224@HA system enables triple inhibition of tumor growth via a combination of targeted therapy and genetic and photodynamic therapy to enhance the therapeutic effects on RCC.

Organometallic Chemistry Tools for Building Biologically Relevant Nanoscale Systems.

The recent emergence of organometallic chemistry for modification of biomolecular nanostructures has begun to rewrite the long-standing assumption among practitioners that small-molecule organometallics are fundamentally incompatible with biological systems. This Perspective sets out to clarify some of the existing misconceptions by focusing on the growing organometallic toolbox for biomolecular modification. Specifically, we highlight key organometallic transformations in constructing complex biologically relevant systems on the nanomolecular scale, and the organometallic synthesis of hybrid nanomaterials composed of classical nanomaterial components combined with biologically relevant species. As research progresses, many of the challenges associated with applying organometallic chemistry in this context are rapidly being reassessed. Looking to the future, the growing utility of organometallic transformations will likely make them more ubiquitous in the construction and modification of biomolecular nanostructures.

Not All Fluctuations Are Created Equal: Spontaneous Variations in Thermodynamic Function

We identify macroscopic functioning arising during a thermodynamic system’s typical and atypical behaviors, thereby describing system operations over the entire set of fluctuations. We show how to use the information processing second law to determine functionality for atypical realizations and how to calculate the probability of distinct modalities occurring via the large-deviation rate function, extended to include highly correlated, memoryful environments and systems. Altogether, the results complete a theory of functional fluctuations for complex thermodynamic nanoscale systems operating over finite periods. In addition to constructing the distribution of functional modalities, one immediate consequence is a cautionary lesson: ascribing a single, unique functional modality to a thermodynamic system, especially one on the nanoscale, can be misleading, likely masking an array of simultaneous, parallel thermodynamic transformations that together may also be functional. In this way, functional fluctuation theory alters how we conceive of the operation of biological cellular processes, the goals of engineering design, and the robustness of evolutionary adaptation.

An (AlN/GaN)N D (AlN/GaN)N Photonic Crystal-based Gas Sensor

Over the past few years, more studies have been conducted on the use of photonic crystals (PCs) in the detection field. Particularly fascinating for use as gas sensors are these materials’ outstanding spectrum sensitivity and small design. Using one-dimensional PCs as the theoretical foundation, this work aims to develop and analyze a nanoscale system that can identify the concentration of gases in ambient air and differentiate it from contaminated air. The intended structure is composed of layers of gallium nitride (GaN) and aluminum nitride (AlN) that alternate. In between these layers is a defective layer cavity that is filled with polluted air, which has a refractive index that is quite similar to pure air. The transfer matrix method (TMM) was used to perform numerical results for the proposed sensor. This sensor achieves average sensitivity of 1791 nm/RIU, average quality factor and figure of merit (FoM) of 1833 and 2287, respectively. We therefore think that the suggested detector’s design offers a strong candidate for accurate and efficient detection.

Statement of Retraction: Application of particle swarm optimization, and genetic algorithm methods for maximizing the phase velocity in the multi-layer nanoscale system

Statement of Retraction: Application of particle swarm optimization, and genetic algorithm methods for maximizing the phase velocity in the multi-layer nanoscale system

A molecular dynamics simulation study of EthylChlorophyllide A molecules confined in a SiO2 nanoslit.

This paper investigates the dynamic behavior of EthylChlorophyllide A (EChlideA) molecules in a methanol solution confined within a 4nm silica nanoslit, using molecular dynamics simulations over a duration of 1ms. Three systems, containing 1, 2, and 4 solutes, were studied at 298K. The results demonstrate that EChlideA molecules predominantly adsorb onto the silica surfaces, driven by specific interactions between chlorin ring's methyl group and the hydroxyl groups of the silica. This adsorption leads to stable binding, particularly in less crowded environments, as indicated by the potential of mean force analysis. Higher molecular concentrations, such as those with four EChlideA molecules, introduce variation in binding strength due to molecular aggregation and complex interactions. The orientation analysis reveals that the chlorin ring tends to align parallel to the surface, requiring rotational adjustments during surface diffusion. In addition, solvent coordination around the Mg ion remains consistent under bulk conditions, although with some variation in higher concentrations. This study also highlights a decrease in linear diffusion and an increase in rotational relaxation times for EChlideA molecules within the confined nanoslit, reflecting the influence of molecular concentration and arrangement on their dynamics. These findings provide valuable insights into the role of surface interactions, molecular orientation, and solvent coordination in confined environments, offering implications for the design of nanoscale systems.

Identifying Rare Events in Quantum Molecular Dynamics of Nanomaterials with Outlier Detection Indices.

Nanoscale and condensed matter systems evolve on multiple length- and time-scales, and rare events such as local phase transformation, ion segregation, defect migration, interface reconstruction, and grain boundary sliding can have a profound influence on material properties. We demonstrate how outlier detection indices can be used to identify rare events in machine-learning based, high-dimensional molecular dynamics (MD) simulations. Designed to order data-points from typical to untypical, the indices enable one to capture atomic events that are hard to detect otherwise. We demonstrate the approach with a nanosecond MD simulation of a grain boundary in a metal halide perovskite that is extensively studied for solar energy and optoelectronic applications. The method captures the initial grain boundary sliding and a spontaneous fluctuation half a nanosecond later, both events giving rise to persistent deep electronic trap states that impact charge carrier lifetime and transport and material performance. The approach offers a generalizable and simple method for identifying outlier events in complex condensed matter, molecular, and nanoscale systems.

Extreme-value analysis in nano-biological systems: applications and implications

AbstractExtreme value analysis (EVA) is a statistical method that studies the properties of extreme values of datasets, crucial for fields like engineering, meteorology, finance, insurance, and environmental science. EVA models extreme events using distributions such as Fréchet, Weibull, or Gumbel, aiding in risk prediction and management. This review explores EVA’s application to nanoscale biological systems. Traditionally, biological research focuses on average values from repeated experiments. However, EVA offers insights into molecular mechanisms by examining extreme data points. We introduce EVA’s concepts with simulations and review its use in studying motor protein movements within cells, highlighting the importance of in vivo analysis due to the complex intracellular environment. We suggest EVA as a tool for extracting motor proteins’ physical properties in vivo and discuss its potential in other biological systems. While there have been only a few applications of EVA to biological systems, it holds promise for uncovering hidden properties in extreme data, promoting its broader application in life sciences.

Insights into the formulation of lipid nanoparticles for the optimization of mRNA therapeutics.

mRNA-based therapeutics increasingly demonstrate significant potential in treating various diseases, including infectious diseases, cancers, and genetic disorders. Effective delivery systems are crucial for advancing mRNA therapeutics. Lipid nanoparticles (LNPs) serve as an excellent carrier, widely validated for their safety and tolerability in commercially available mRNA vaccines. Standard LNPs typically consist of four components: ionizable lipids (ILs), helper lipids, cholesterol, and polyethylene glycol-lipids (PEG-lipids), with the structural design of ILs gradually becoming a focal point of research interest. The chemical structures and formulations of the other components also significantly affect the delivery efficiency, targeting specificity, and stability of LNPs. The complex formulations of LNPs may hinder the clinical transformation of mRNA therapeutics and have raised widespread concerns about their safety. This review aims to summarize the progress of LNPs-based mRNA therapeutics in clinical trials, focusing on adverse effects that occurred during these trials. It also discusses representative innovations in LNP components, highlighting challenges and potential ways in this research field. We firmly believe this review will promote further improvements and designs of LNP compositions to optimize mRNA therapeutics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures.

Polyester nanoparticles delivering chemotherapeutics: Learning from the past and looking to the future to enhance their clinical impact in tumor therapy.

Polymeric nanoparticles (NPs), specifically those comprised of biodegradable and biocompatible polyesters, have been heralded as a game-changing drug delivery platform. In fact, poly(α-hydroxy acids) such as polylactide (PLA), poly(lactide-co-glycolide) (PLGA), and poly(ε-caprolactone) (PCL) have been heavily researched in the past three decades as the material basis of polymeric NPs for drug delivery applications. As materials, these polymers have found success in resorbable sutures, biodegradable implants, and even monolithic, biodegradable platforms for sustained release of therapeutics (e.g., proteins and small molecules) and diagnostics. Few fields have gained more attention in drug delivery through polymeric NPs than cancer therapy. However, the clinical translational of polymeric nanomedicines for treating solid tumors has not been congruent with the fervor or funding in this particular field of research. Here, we attempt to provide a comprehensive snapshot of polyester NPs in the context of chemotherapeutic delivery. This includes a preliminary exploration of the polymeric nanomedicine in the cancer research space. We examine the various processes for producing polyester NPs, including methods for surface-functionalization, and related challenges. After a detailed overview of the multiple factors involved with the delivery of NPs to solid tumors, the crosstalk between particle design and interactions with biological systems is discussed. Finally, we report state-of-the-art approaches toward effective delivery of NPs to tumors, aiming at identifying new research areas and re-evaluating the reasons why some research avenues have underdelivered. We hope our effort will contribute to a better understanding of the gap to fill and delineate the future research work needed to bring polyester-based NPs closer to clinical application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Experimental Verification of Demon-Involved Fluctuation Theorems.

The limit of energy saving in the control of small systems has recently attracted much interest due to the concept refinement of the Maxwell demon. Inspired by a newly proposed set of fluctuation theorems, we report the first experimental verification of these equalities and inequalities in an ultracold ^{40}Ca^{+} ion system, confirming the intrinsic nonequilibrium in the system due to involvement of the demon. Based on elaborately designed demon-involved control protocols, such as the Szilard engine protocol, we provide experimentally quantitative evidence of the dissipative information and observe tighter bounds of both the extracted work and the demon's efficacy than the limits predicted by the Sagawa-Ueda theorem. Our results substantiate a close connection between the physical nature of information and nonequilibrium processes at the microscale, which help to further understand the thermodynamic characteristics of information and the optimal design of nanoscale and smaller systems.

Novel Approaches and Applications of Nanotechnology in the Delivery of Topical Drugs for Psoriasis via Nanocarriers

Psoriasis is a non-contagious, continuing, auto-immune disease that mostly affects the skin, and about 2%-3% of the world's population suffers from it. In this review article, the primary focus is on the strategies involved in conventional therapies and the latest advances that have been recorded in metallic nano, polymer-based, and lipid-based formulations in the spectrum of anti-psoriatic drugs. Liposomes, ethosomes, solid lipid nanoparticles, micelles, and dendrimers are only some of the nanocarrier systems that have been extensively researched in relation to their potential use in nano formulations. This study incorporates patent applications that illustrate the nanoparticle's function in treating psoriasis. Hence, on the basis of an extensive literature survey, it is concluded that nano-formulations are a promising medium to treat a disease like psoriasis as they offer enhanced penetration, target-specific delivery, and improved efficacy. When applied to the study of biological systems and the development of novel medical technologies, nanobiotechnology offers potentially promising possibilities for the efficient use of nanoscale materials and processes. In this approach, nanotechnology and biotechnology are combined in order to develop nanoscale devices, materials, and systems that can be used for the diagnosis, treatment, and prevention of psoriasis. The future of the therapeutic effect of antipsoriatic drugs is dependent on both the benefits they have the ability to bring and the progress being made in the mass production of these carriers. Researching novel carrier systems or combination therapies is essential, but so is working to scale up existing technologies so they may be commercialised and used to benefit society at large.

Synergetic Sonodynamic-Immunotherapy based on phycocyanin nanoparticles (PCNP) reduces tumor growth and metastasis in mice

Sonodynamic-immunotherapy as a combined treatment offers a synergistic effect for tumor growth and metastasis reduction. The concise, manufacturable, multifunctional nanosystems are the key to implementing this strategy. In this article, we report the development of a novel nanoscale system based on phycocyanin nanoparticles (PCNP) for the co-delivery of the immunoadjuvant hydrochloride imiquimod (R837(hy)), achieving a dual role as both sonosensitizer and immunomodulatory agent. Our findings demonstrate that PCNP-mediated SDT can trigger immunogenic cell death (ICD) in tumor cells, releasing tumor-associated antigens and simultaneously delivering R837(hy) to effectively activate the immune response. This process results in the maturation of dendritic cells and leading to a potent and targeted antitumor immune response. When combined with the cytotoxic T-lymphocyte antigen 4 (CTLA-4) checkpoint blockade, this strategy significantly reduces tumor growth and metastasis in murine models, with minimal systemic toxicity. Our approach effectively integrates sonodynamics and immunotherapy for the treatment and prevention of cancer recurrence through the PCNP-R837(hy) system, offering a promising strategy to overcome the limitations of current therapies.

Planar Disk μ-Aptasensors by Monolayer Assembly in a Dissolving Microdroplet.

Electrochemical aptamer-based sensors provide a highly modular platform for real-time monitoring of small molecules. Their ability to selectively recognize target molecules in complex environments like biological fluids makes them an attractive technology for the analysis of micro- and nanoscale systems. The signal-to-noise of the measurement depends on the electroactive surface (i.e., how many aptamers one can place), which has previously precluded miniaturization of aptamer-based sensors to planar disk ultramicroelectrodes (r ∼ 5-10 μm). Here, we employ a concentration enrichment strategy based on the active dissolution of an aqueous, aptamer-containing microdroplet on an ultramicroelectrode submerged in an organic continuous phase (1,2-dichloroethane). We show consistent voltammetric signal increase as a function of droplet lifetime, indicating the successful immobalization of the thiol-terminated aminoglycoside aptamers to the electrode surface. We observe a diagnostic methylene blue peak and 10-fold increase in current magnitude as compared to bare microelectrodes. We report robust sensor behavior with a linear dynamic range extending from milli- to micromolar concentrations of kanamycin in buffer. This research offers a successful method for optimized electrochemical aptamer-based sensor fabrication and miniaturization on ultramicroelectrodes without the need for electrode surface area enhancement.

Size-Dependent Ab Initio Atomistic Thermodynamics from Cluster to Bulk: Application to Hydration of Titania Nanoparticles.

Ab initio atomistic thermodynamics (AIAT) has become an indispensable tool to estimate Gibbs free energy changes for solid surfaces interacting with gaseous species relative to pressure (p) and temperature (T). For such systems, AIAT assumes that solid vibrational contributions to Gibbs free energy differences cancel out. However, the validity of this assumption is unclear for nanoscale systems. Using hydrated titania nanoparticles (NPs) as an example, we estimate the vibrational contributions to the Gibbs free energy of hydration (ΔGhyd(T,p)) for arbitrary NP size and degree of hydration. Comparing ΔGhyd(T,p) phase diagrams for NPs when considering these contributions (AIATnano) relative to a standard AIAT approach reveals significant qualitative and quantitative differences, which only become negligible for large systems. By constructing a size-dependent ΔGhyd(T,p) phase diagram, we illustrate how our approach can provide deeper insights into how nanosytems interact with their environments, with many potential applications (e.g., catalytic nanoparticles, biological colloids, nanoparticulate pollutants).

Geometry-induced friction at a soft interface

Soft and biological matter come in a variety of shapes and geometries. When soft surfaces that do not fit into each other due to a mismatch in Gaussian curvatures form an interface, beautiful geometry-induced patterns are known to emerge. In this paper, we study the effect of geometry on the dynamical response of soft surfaces moving relative to each other. Using a simple experimental scheme, we measure friction between a highly bendable thin polymer sheet and a hydrogel substrate. At this soft and low-friction interface, we find a strong dependence of friction on the relative geometry of the two surfaces-a flat sheet experiences significantly larger friction on a spherical substrate than on flat or cylindrical substrate. We show that the stress developed in the sheet due to its geometrically incompatible confinement is responsible for the enhanced friction. This mechanism also leads to a transition in the nature of friction as the sheet radius is increased beyond a critical value. Our finding reveals a hitherto unnoticed mechanism based on an interplay between geometry and elasticity that may influence friction significantly in soft, biological, and nanoscale systems. In particular, it provokes us to reexamine our understanding of phenomena such as the curvature dependence of biological cell mobility.

Visualization of Microcapillary Tips Using Waveguided Light.

The microcapillary, a glass tube with a nano/micrometer scale aperture, is used for manipulating small objects across diverse disciplines. A primary concern in using the microcapillary involves tip breakage upon contact. Here, we report a method for visualizing the microcapillary tip, enabling precise and instant determination of its contact with other objects. Illumination directed to the back aperture of the microcapillary induces waveguiding through the glass wall, enabling the visualization of the tip through scattering. We demonstrate that the tip scattering is sensitive to contact with an adjacent object owing to the near-field interaction of the waveguided light, providing a clear distinction between the contact and noncontact states. The key advantage of our method encompasses its minimal influence, irrespective of conductivity, and applicability to nanoscale systems. The versatility of our method is shown by the application to a wide range of tip diameters, various substrate and in-filling materials.

Accurate and efficient prediction of optical gaps in silicon and germanium nanoparticles using a high-local-exchange density functional

We investigated the HOMO-LUMO gaps and the optical gaps of Si and Ge nanoparticles (NPs) with various terminations and sizes using different functionals (HLE16, B3LYP, HSE-HJS) and basis sets (CRENBL, def2-SVP, def2-TZVP). The high-local-exchange functional HLE16, without Hartree–Fock exchange, effectively reproduces optical gaps using HOMO−LUMO gaps, offering a cost-effective alternative to hybrid functionals and TDDFT in nanoscale systems. Size (quantum confinement effects) and termination ligands (surface effects) significantly impact energy gaps: nonpolar CH3 had minimal effects, while polar ligands reduced gaps notably. Finally, ECP basis sets like CRENBL are better suited for NP electronic structures than all-electron basis sets.

Bioinspired and bioderived nanomedicine for inflammatory bowel disease.

Due to its chronic nature and complex pathophysiology, inflammatory bowel disease (IBD) poses significant challenges for treatment. The long-term therapies for patients, often diagnosed between the ages of 20 and 40, call for innovative strategies to target inflammation, minimize systemic drug exposure, and improve patients' therapeutic outcomes. Among the plethora of strategies currently pursued, bioinspired and bioderived nano-based formulations have garnered interest for their safety and versatility in the management of IBD. Bioinspired nanomedicine can host and deliver not only small drug molecules but also biotherapeutics, be made gastroresistant and mucoadhesive or mucopenetrating and, for these reasons, are largely investigated for oral administration, while surprisingly less for rectal delivery, recommended first-line treatment approach for several IBD patients. The use of bioderived nanocarriers, mostly extracellular vesicles (EVs), endowed with unique homing abilities, is still in its infancy with respect to the arsenal of nanomedicine under investigation for IBD treatment. An emerging source of EVs suited for oral administration is ingesta, that is, plants or milk, thanks to their remarkable ability to resist the harsh environment of the upper gastrointestinal tract. Inspired by the unparalleled properties of natural biomaterials, sophisticated avenues for enhancing therapeutic efficacy and advancing precision medicine approaches in IBD care are taking shape, although bottlenecks arising either from the complexity of the nanomedicine designed or from the lack of a clear regulatory pathway still hinder a smooth and efficient translation to the clinics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.