Nanoscale Systems Research Articles

Protein cargo encapsulation by virus-like particles: Strategies and applications.

Viruses and the recombinant protein cages assembled from their structural proteins, known as virus-like particles (VLPs), have gained wide interest as tools in biotechnology and nanotechnology. Detailed structural information and their amenability to genetic and chemical modification make them attractive systems for further engineering. This review describes the range of non-enveloped viruses that have been co-opted for heterologous protein cargo encapsulation and the strategies that have been developed to drive encapsulation. Spherical capsids of a range of sizes have been used as platforms for protein cargo encapsulation. Various approaches, based on native and non-native interactions between the cargo proteins and inner surface of VLP capsids, have been devised to drive encapsulation. Here, we outline the evolution of these approaches, discussing their benefits and limitations. Like the viruses from which they are derived, VLPs are of interest in both biomedical and materials applications. The encapsulation of protein cargo inside VLPs leads to numerous uses in both fundamental and applied biocatalysis and biomedicine, some of which are discussed herein. The applied science of protein-encapsulating VLPs is emerging as a research field with great potential. Developments in loading control, higher order assembly, and capsid optimization are poised to realize this potential in the near future. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Engineering metal-phenolic networks for enhancing cancer therapy by tumor microenvironment modulation.

The complicated tumor microenvironment (TME) is featured by low pH values, high redox status, and hypoxia, which greatly supports the genesis, development, and metastasis of tumors, leading to drug resistance and clinical failure. Moreover, a lot of immunosuppressive cells infiltrate in such TME, resulting in depressing immunotherapy. Therefore, the development of TME-responsive nanoplatforms has shown great significance in enhancing cancer therapeutics. Metal-phenolic networks (MPNs)-based nanosystems, which self-assemble via coordination of phenolic materials and metal ions, have emerged as excellent TME theranostic nanoplatforms. MPNs have unique properties including fast preparation, tunable morphologies, pH response, and biocompatibility. Besides, functionalization and surface modification can endow MPNs with specific functions for application requirements. Here, the representative engineering strategies of various polyphenols are first introduced, followed by the introduction of the engineering mechanisms of polyphenolic nanosystems, fabrication, and distinct properties of MPNs. Then, their advances in TME modulation are highlighted, such as antiangiogenesis, hypoxia relief, combination therapy sensitization, and immunosuppressive TME reversion. Finally, we will discuss the challenges and future perspectives of MPNs-based nanosystems for enhancing cancer therapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanoparticle-peptide conjugates for bacterial detection and neutralization: Potential applications in diagnostics and therapy.

Infections caused by antibiotic-resistant bacteria continue to challenge the medical field, mostly due to conventional treatments inefficiency after years of overuse and misuse in clinics. Cases of multiresistant bacterial infections are increasing every year. This led the World Health Organization (WHO) to update the list of resistant micro-organisms that represent greatest threat to human health. To stop the growing of the global resistance to antimicrobial drugs, new alternatives are necessary to fight these pathogens. In this context, antimicrobials peptides (AMPs) emerge as a new alternative to the current antibiotics in the pharmaceutical market. To improve their antimicrobial activity, different strategies are being developed to overcome antibiotic-resistant bacteria. Nanotechnology can be used to further potentiate antimicrobials, by increasing their activity or assisting in their delivering, frequently using nanostructured materials. There are already several antimicrobial peptides used in therapeutics, some of them coupled to nanoparticles. Additionally, detection strategies taking advantage of peptides as recognition agents are also being explored. Several examples are detailed of peptides that are specific to bacterial targets, and how that specificity can be used in diagnostics systems, coupled with nanoparticles-based signal detection approaches. Thus, the same properties of AMPs that enable specific neutralization can be harnessed to detect the very same bacteria they target. Overall, this review is focused on current research on nanoparticles coupled to antimicrobial peptides and how they can be used against multidrug-resistant bacteria as antimicrobials and/or as detection system. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Glycoprotein Ib-regulated micro platelet ghost for biosafe distribution and photothermal oncotherapy

Despite the tremendous theranostics potential of nano-scale drug delivery system (NDDS) in oncology field, their tumor-targeting efficiency and safety remain major challenges due to their proneness of off-target accumulation through widespread vascular endothelial gaps (up to 1μm). To address this problem, in this research, micro-sized cellular platelet "ghosts" (PGs, 1.32μm, platelet without inner granules and coagulation) were employed as carriers to ship hollow gold nanoparticles (HGNs, 58.7nm), forming a hierarchical biosafe system (PG@HGNs) to reduce normal tissue interception and enhance tumor targeting delivery of HGNs for improved photothermal therapy. PGs were prepared by an optimized "swelling-extrusion-elution" method, HGNs were loaded in PGs (PG@HGNs) through a "hypotonic dialysis" method and the safety and biodistribution of the system was evaluated in vitro and in vivo. In in vitro condition that stimulated the tumoral vessel acidic microenvironment (pH=6.5), PG@HGNs were demonstrated with enhanced membrane fluidity through down-regulation of the glycoprotein Ib expressed on the PGs. This change induced a burst release of nano-sized HGNs which were capable to traverse vascular endothelium layer on a tumor-endothelial cell transwell model, whilst the micro-sized PG carriers were intercepted. In comparison to nano-sized platelet membrane-coated carriers (PM@HGNs), PG@HGNs showed enhanced internalization and cytotoxicity to 4T1 cells. In animal models, PG@HGNs remarkably prolonged circulation most likely due to the presence of "self-recognition" receptor-CD47 of PGs, and effectively reduced normal tissue interception via the micro-scale size effect. These both contributed to the significantly improved tumor targeting efficiency of HGNs. PG@HGNs generated the greater antitumor photothermal efficacy alongside safety in the animals compared to PM@HGNs. Collectively, this study demonstrated the potential of the micro-scale PGs equipped with adjusted membrane GP Ib as biosafe vehicles for HGNs or possibly other nanodrugs. THE STATEMENT OF SIGNIFICANCE: Despite the tremendous theranostics potentials, the safety and tumor-targeting efficiency of nano-scale drug delivery systems (NDDS) are compromised by their undesirable accumulation in normal tissues with widespread vascular endothelial gaps, such as many tumor-targeted NDDSs still accumulated much in liver and/or spleen. Herein, we explored a micro-nano biomimetic cascade delivery system to address the above drawbacks. By forming a hierarchical biosafe system, micro-sized platelet "ghost" (PGs, 1.32μm) was employed as tumor-targeted delivery carrier to transport hollow gold nanoparticles (HGNs, 58.7nm). It was demonstrated that this micro-size system could maintain platelet membrane structure thus prolong in vivo circulation, while avoiding extravasation into normal tissues. PG@HGNs could sensitively respond to the acidic microenvironment near tumor vessel via down-regulation of glycoprotein Ib and rapidly release "nano-bullets"-HGNs to further penetrate into the tumor tissues through EPR effect, thus enhancing photothermal efficacy generated by HGNs under NIR irradiation. Collectively, the micro-scaled PGs could be biosafe vehicles for improved tumor-targeted delivery of HGNs or possibly other nanodrugs.

Phononic heat conductance of gold atomic contacts: Coherent versus incoherent transport

We present here a theoretical method to determine the phononic contribution to the thermal conductance of nanoscale systems in the phase-coherent regime. Our approach makes use of classical molecular dynamics (MD) simulations to calculate the temperature-dependent dynamical matrix, and the phononic heat conductance is subsequently computed within the Landauer-B\"uttiker formalism with the help of nonequilibrium Green's function techniques. Tailored to nanostructures, crucial steps of force constant and heat transport calculations are performed directly in real space. As compared to conventional density functional theory (DFT) approaches, the advantage of our method is two-fold. First, interatomic interactions can be described with the method of choice. Semiempirical potentials may lead to large computational speedups, enabling the study of much larger systems. Second, the method naturally takes into account the temperature dependence of atomic force constants, an aspect that is ignored in typical static DFT-based calculations. We illustrate our method by analyzing the temperature dependence of the phononic thermal conductance of gold (Au) chains with lengths ranging from 1 to 12 atoms. Moreover, in order to evaluate the importance of anharmonic effects in these atomic-scale wires, we compare the phase-coherent approach with nonequilibrium MD (NEMD) simulations. We find that the predictions of the phase-coherent method and the classical NEMD approach largely agree above the Debye temperature for all studied chain lengths, which shows that heat transport is coherent and that our phase-coherent approach is well suited for such nanostructures.

Overcoming PEG─Protein Mutual Repulsion to Improve the Efficiency of PEGylation.

Bioconjugation reactions, such as protein PEGylation, generally require excess reagents because of their inefficiency. Intriguingly, few reports have investigated the fundamental causes of this inefficiency. This study demonstrates that the excluded volume effect (EVE)─caused by the mutual repulsion of methoxy poly(ethylene glycol) (mPEG) and proteins under typical PEGylation conditions─causes proteins and protein-reactive mPEG (5 kDa) to self-associate into separate "protein-rich" and "mPEG-rich" nano-domains (i.e., soluble self-assemblies). To overcome this obstacle to reaction, "unreactive" low-molecular-weight mPEG was added as a co-solvent to promote the association between the larger protein and the reactive mPEG molecules by harnessing the same EVE. The near complete PEGylation of lysozyme could be achieved with close to stoichiometric amounts of reactive mPEG, and beneficial effects were observed for other proteins. Considering the general nature of the EVE (e.g., salting-out and PEGying-out), this study provides important perspectives on enhancing bioconjugation reactions, which are relevant to many nanoscale systems.

Nanotherapy based on magneto-mechanochemical modulation of tumor redox state.

Magnetic nanoparticles (MNs) are typically used as contrast agents for magnetic resonance imaging or as drug carriers with a remotely controlled delivery to the tumor. However, they can also potentiate the action of anticancer drugs under the influence of applied constant magnetic (CMFs) and electromagnetic fields (EMFs). This review demonstrates the role of magneto-mechanochemical effects produced by MNs alone and loaded with anticancer agents (MNCs) in response to CMFs and EMFs for modulation of tumor redox state. The combined treatment is suggested to act by two mechanisms: spin-dependent electron transport propagates free radical chain reactions, while magnetomechanical interactions cause conformational changes in drug molecules loaded onto MNs and generate reactive oxygen species (ROS). By adjusting the parameters of CMFs and EMFs during the magneto-mechanochemical synthesis and subsequent treatment, it is possible to modulate ROS production and switch redox signaling involved in ERK1/2 and NF-κB pathways from initiation of tumor growth to inhibition. Observations of tumor volume in different animal models and treatment combinations reported a 6%-70% reduction as compared with conventional drugs. Despite these results, there is a general lack of research in magnetic nanotheranostics that link redox changes across multiple levels of organization in the tumor-bearing host. Further multidisciplinary studies with more focus on the relationship between the electron transport processes in biomolecules and their effects on the tumor-host interaction should accelerate the clinical translation of magnetic nanotheranostics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Switching in Nanoscale Molecular Junctions due to Contact Reconfiguration

Switching effects are key elements in the design and characterization of nanoscale molecular electronics systems. They are used to achieve functionality through the transition between different conducting states. In this study, we analyze the presence of switching events in reference molecular systems, which are not designed to have switching behavior, such as oligo(phenylene ethynylene)s and alkanes, using the mechanically controllable break junction technique. These events can be classified in two groups, depending on whether the breaking trace shows exponential decay or plateau-like features before the switch happens. We argue that the former correspond to junctions forming after rupture of the gold atomic point contact, while the latter can be related to a change in the contact geometry of the junction. These results highlight how a proper choice of anchoring group and careful comparison with reference compounds are essential to understanding the origin of switching in molecular break junctions.

Advances in design of polymer brush functionalized inorganic nanomaterials and their applications in biomedical arena.

Grafting of polymer brush (assembly of polymer chains tethered to the substrate by one end) is emerging as one of the most viable approach to alter the surface of inorganic nanomaterials. Inorganic nanomaterials despite their intrinsic functional superiority, their applications remain restricted due to their incompatibility with organic or biological moieties vis-à-vis agglomeration issues. To overcome such a shortcoming, polymer brush modified surfaces of inorganic nanomaterials have lately proved to be of immense potential. For example, polymer brush-modified inorganic nanomaterials can act as efficient substrates/platforms in biomedical applications, ranging from drug-delivery to protein-array due to their integrated advantages such as amphiphilicity, stimuli responsiveness, enhanced biocompatibility, and so on. In this review, the current state of the art related to polymer brush-modified inorganic nanomaterials focusing, not only, on their synthetic strategies and applications in biomedical field but also the architectural influence of polymer brushes on the responsiveness properties of modified nanomaterials have comprehensively been discussed and its associated future perspective is also presented. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Ultrafast valley polarization of graphene nanorings

We study theoretically electron dynamics of a graphene nanoring placed in the field of an ultrashort optical pulse. We describe the graphene nanoring within an effective model with infinite mass boundary conditions. For an optical pulse with a duration of just a few femtoseconds, the electron dynamics is coherent and is described by a time-dependent Schr\"odinger equation. If the optical pulse is circularly polarized, then two valleys of graphene are populated differently, resulting in a finite valley polarization of the system after the pulse. Such a valley polarization is a unique property of graphene nanoscale systems, while for a graphene monolayer, a circularly polarized pulse does not produce any valley polarization. The valley polarization of the graphene nanoring depends on parameters of the system, such as inner and outer radii. With the system's size increasing, the valley polarization monotonically decreases, converging to its zero value for the infinite graphene monolayer.

Computing Thermodynamic Properties of Fluids Augmented by Nanoconfinement: Application to Pressurized Methane.

Nanoconfined fluids exhibit remarkably different thermodynamic behavior compared to the bulk phase. These confinement effects render predictions of thermodynamic quantities of nanoconfined fluids challenging. In particular, confinement creates a spatially varying density profile near the wall that is primarily responsible for adsorption and capillary condensation behavior. Significant fluctuations in thermodynamic quantities, inherent in such nanoscale systems, coupled to strong fluid-wall interactions give rise to this near-wall density profile. Empirical models have been proposed to explain and model these effects, yet no first-principles based formulation has been developed. We present a statistical mechanics framework that embeds such a coupling to describe the effect of the fluid-wall interaction in amplifying the near-wall density behavior for compressible gases at elevated pressures such as pressurized methane in confinement. We show that the proposed theory predicts accurately the adsorbed layer thickness as obtained with small-angle neutron scattering measurements. Furthermore, the predictions of density under confinement from the proposed theory are shown to be in excellent agreement with available experimental and atomistic simulations data for a range of temperatures for nanoconfined methane. While the framework is presented for evaluating the near-wall density, owing to its rigorous foundation in statistical mechanics, the proposed theory can also be generalized for predicting phase-transition and nonequilibrium transport of nanoconfined fluids.

Locally Structured On-Chip Optofluidic Hollow-Core Light Cages for Single Nanoparticle Tracking.

Nanoparticle tracking analysis (NTA) is a widely used methodology to investigate nanoscale systems at the single species level. Here, we introduce the locally structured on-chip optofluidic hollow-core light cage, as a novel platform for waveguide-assisted NTA. This hollow waveguide guides light by the antiresonant effect in a sparse array of dielectric strands and includes a local modification to realize aberration-free tracking of individual nano-objects, defining a novel on-chip solution with properties specifically tailored for NTA. The key features of our system are (i) well-controlled nano-object illumination through the waveguide mode, (ii) diffraction-limited and aberration-free imaging at the observation site, and (iii) a high level of integration, achieved by on-chip interfacing to fibers. The present study covers all aspects relevant for NTA including design, simulation, implementation via 3D nanoprinting, and optical characterization. The capabilities of the approach to precisely characterize practically relevant nanosystems have been demonstrated by measuring the solvency-induced collapse of a nanoparticle system which includes polymer brush-based shells that react to changes in the liquid environment. Our study unlocks the advantages of the light cage approach in the context of NTA, suggesting its application in various areas such as bioanalytics, life science, environmental science, or nanoscale material science in general.

Interfacial skin modes at a non-Hermitian heterojunction

We uncover a non-Hermitian skin mode in which the eigenmodes of a nonreciprocal topoelectrical (TE) heterojunction circuit array are localized at the heterojunction interface under both open boundary condition (OBC) and periodic boundary condition (PBC). This is in marked contrast to the conventional non-Hermitian skin effect (NHSE) in homogenous non-Hermitian systems that exists under OBC but vanishes in PBC. The interfacial non-Hermitian skin effect is induced when two non-Hermitian circuit chain segments with dissimilar NHSE decay lengths are cascaded together. It is shown analytically that the interfacial NHSE decay rates are directly associated with the asymmetric intracell couplings in the TE segments. Such nonreciprocal directional couplings can be realized in practical circuits by means of negative impedance converters with current inversion (INIC). In contrast to the conventional NHSE in homogeneous systems, the TE heterojunction circuit allows for a voltage profile localized at the interface, that is independent of the boundary conditions and whose decay length can be modulated by circuit parameters. Finally, the results presented are general and applicable to other analogous non-Hermitian platforms such as photonic and condensed matter nanoscale systems.

Designing High Entropy Amorphous Oxides for Li-Battery Electrolytes

Amorphous Li-oxides such as LiPON and amorphous Li garnet are considered as promising solid-state electrolytes for use in hybrid or all-solid-state oxide- and sulfide-based batteries as separators or protective layers.1-3 These materials possess several appealing characteristics, such as their intrinsic grain-boundary-free nature and relatively low manufacturing temperature (ranging from room temperature to 600 °C), which facilitates co-synthesis with Co-substituted or even Co-free cathodes that are unstable at standard electrolyte sintering temperatures. Alternatively, they can be applied as protective coatings toward Li anodes and other Li-free anode concepts, bridging the electrochemical stability voltage gap with liquid electrolytes or catholytes and preventing uneven interfacial reactions. The amorphous Li-oxides can be classified based on their structural entropy, i.e., the number and types of local bonding units (LBUs). As of today, ‘low entropy’ amorphous LiPON with only one type of LBU achieves the highest cycle number and battery lifetime.4 ‘High entropy’ amorphous Li-ion conductors, such as Li perovskites or Li garnets, exhibit an unusually high number of LBUs. local ordering and the Li-ion dynamics remain poorly understood, in part owing to the difficulty in characterizing their disordered states. This study employed a novel synthesis protocol to stabilize amorphous Al-doped Li garnets, representing so far the highest number of LBUs (≥ 4) in an amorphous Li-ion conductor.5 We resolved their phase evolution and local structures by a combination of spectroscopy, microscopy, and calorimetry techniques. A much wider (<680 °C) but processing-friendly temperature range was identified to stabilize various amorphous phases with edge- and face-sharing Zr, La, and Li LBUs that do not conform to the formation rules for Zachariasen’s glasses. These amorphous Li-ion conductors reveal an unusual setting in which Li and Zr act as network formers and La acts as a network modifier, with the highest Li-dynamics observed for smaller Li–O and Zr–O coordination among the amorphous phases. Our insight provides fundamental guidelines for the phase, local structure, and Li-transport modulation for amorphous Li garnets and pave the way for their integration in next-generation solid-state or hybrid battery designs with enhanced safety and lifetime. Acknowledgments Y.Z. acknowledges financial support provided by the MIT Energy Initiative fellowship offered by ExxonMobil. This research was supported by Samsung Electronics. This research was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), which was supported by the National Science Foundation under NSF award no. 1541959. CNS is a part of Harvard University. This research used resources of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, and was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357, and the Canadian Light Source and its funding partners.

Titanium dioxide nanoparticles: Recent progress in antimicrobial applications.

For decades, the antimicrobial applications of nanoparticles (NPs) have attracted the attention of scientists as a strategy for controlling the ever-increasing threat of multidrug-resistant microorganisms. The photo-induced antimicrobial properties of titanium dioxide (TiO2 ) NPs by ultraviolet (UV) light are well known. This review elaborates on the modern methods and antimicrobial mechanisms of TiO2 NPs and their modifications to better understand and utilize their potential in various biomedical applications. Additional compounds can be grafted onto TiO2 nanomaterial, leading to hybrid metallic or non-metallic materials. To improve the antimicrobial properties, many approaches involving TiO2 have been tested. The results of selected studies from the past few years covering the most recent trends in this field are discussed in this review. There is extensive evidence to show that TiO2 NPs can exhibit certain antimicrobial features with disputable roles of UV light. Hence, they are effective in treating bacterial infections, although the majority of these conclusions came from in vitro studies and in the presence of some additional nanomaterials. The methods of evaluation varied depending on the nature of the research while researchers incorporated different techniques, including determining the minimum inhibitory concentration, cell count, and using disk and well diffusion methods, with a noticeable indication that cell count was the most and dominant criterion used to evaluate the antimicrobial activity. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Nonviral nanoparticle gene delivery into the CNS for neurological disorders and brain cancer applications.

Nonviral nanoparticles have emerged as an attractive alternative to viral vectors for gene therapy applications, utilizing a range of lipid-based, polymeric, and inorganic materials. These materials can either encapsulate or be functionalized to bind nucleic acids and protect them from degradation. To effectively elicit changes to gene expression, the nanoparticle carrier needs to undergo a series of steps intracellularly, from interacting with the cellular membrane to facilitate cellular uptake to endosomal escape and nucleic acid release. Adjusting physiochemical properties of the nanoparticles, such as size, charge, and targeting ligands, can improve cellular uptake and ultimately gene delivery. Applications in the central nervous system (CNS; i.e., neurological diseases, brain cancers) face further extracellular barriers for a gene-carrying nanoparticle to surpass, with the most significant being the blood-brain barrier (BBB). Approaches to overcome these extracellular challenges to deliver nanoparticles into the CNS include systemic, intracerebroventricular, intrathecal, and intranasal administration. This review describes and compares different biomaterials for nonviral nanoparticle-mediated gene therapy to the CNS and explores challenges and recent preclinical and clinical developments in overcoming barriers to nanoparticle-mediated delivery to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

A review on various plant-derived nanoemulgels and their applications

Nanoemulgel is an emergent and promising drug delivery system used nowadays in the pharmaceutical industry. As a novel transdermal drug delivery tool, the applications of nanoemulgel have increasingly been used due to their unique characteristic properties and benefits over other oral and topical drug deliveries to avoid poor drug bioavailability and pharmacokinetic variations. These nanoemulgels are principally oil-in-water nanoemulsions gelled with a certain gelling agent in them. Plant extracts provide remarkable therapeutic options to manage different disease conditions due to their various pharmacological activities such as antioxidant, anti-inflammatory, anti-cancer, antibacterial, etc. However, the poor solubility and low bioavailability of lipophilic phytochemicals in plant extracts are two major issues in developing plant-derived formulations. In the past years, pharmaceutical research has focused more on nano-scale delivery systems to overcome the above problems by improving the delivery of herbal extracts and they have also reported nanoemulgel as a good vehicle for lipophilic and poorly soluble drugs. Therefore, the objective of this review is to discuss recent studies and applications of plant-derived nanoemulgels.

Atomic-Scale Rectification and Inelastic Electron Tunneling Spectromicroscopy.

The phenomenon of rectification describes the emergence of a DC current from the application of an oscillating voltage. Although the origin of this effect has been associated with the nonlinearity in the current-voltage I(V) relation, a rigorous understanding of the microscopic mechanisms for this phenomenon remains challenging. Here, we show the close connection between rectification and inelastic electron tunneling spectroscopy and microscopy for single molecules with a scanning tunneling microscope. While both techniques are based on nonlinear features in the I(V) curve, comprehensive line shape analyses reveal notable differences that highlight the two complementary techniques of nonlinear conductivity spectromicroscopy for probing nanoscale systems.

Visualizing Nanoscale Dynamics with Time-resolved Electron Microscopy

The large number of interactions in nanoscale systems leads to the emergence of complex behavior. Understanding such complexity requires atomic-resolution observations with a time resolution that is high enough to match the characteristic timescale of the system. Our laboratory’s method of choice is time-resolved electron microscopy. In particular, we are interested in the development of novel methods and instrumentation for high-speed observations with atomic resolution. Here, we present an overview of the activities in our laboratory.

Chitosan-based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy.

Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of thebiocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation.