Size-Dependent Penetration of Nanoparticles in Tumor Spheroids: A Multidimensional and Quantitative Study of Transcellular and Paracellular Pathways.

Tumor penetration of nanoparticles is crucial in nanomedicine, but the mechanisms of tumor penetration are poorly understood. This work presents a multidimensional, quantitative approach to investigate the tissue penetration behavior of nanoparticles, with focuses on the particle size effect on penetration pathways, in an MDA-MB-231 tumor spheroid model using a combination of spectrometry, microscopy, and synchrotron beamline techniques. Quasi-spherical gold nanoparticles of different sizes are synthesized and incubated with 2D and 3D MDA-MB-231 cells and spheroids with or without an energy-dependent cell uptake inhibitor. The distribution and penetration pathways of nanoparticles in spheroids are visualized and quantified by inductively coupled plasma mass spectrometry, two-photon microscopy, and synchrotron X-ray fluorescence microscopy. The results reveal that 15 nm nanoparticles penetrate spheroids mainly through an energy-independent transcellular pathway, while 60 nm nanoparticles penetrate primarily through an energy-dependent transcellular pathway. Meanwhile, 22 nm nanoparticles penetrate through both transcellular and paracellular pathways and they demonstrate the greatest penetration ability in comparison to other two sizes. The multidimensional analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nanoparticles, and the results provide important insights into the designs of nanoparticles with high accumulation at a target site.

Polyphenol-Mediated Liquid Metal Composite Architecture for Solar Thermoelectric Generation.

The development of advanced solar energy technologies, which efficiently convert solar energy to heat and then to electricity, remains a significant challenge in the pursuit of clean energy production. Here, this challenge is addressed by designing a photothermal absorber composed of liquid gallium particles and a natural polyphenol-based coordination ink. The design of this composite takes advantage of the tuneable light absorption properties of the polyphenol inks and can also be applied onto flexible substrates. While the ink utilizes two types of coordination complexes to absorb light at different wavelengths, the liquid gallium particles with high thermal and electrical properties provide enhanced thermoelectric effect. As such, the photothermal composite exhibits a broad-spectrum light absorption and highly efficient solar-to-heat conversion. A thermoelectric generator coated with the photothermal composite exhibits an impressive voltage output of ≈185.3 mV when exposed to 1 Sun illumination, without requiring any optical concentration, which sets a new record for a power density at 345.5 µW cm-2 . This work showcases the synergistic combination of natural compound-based light-absorbing coordination complexes with liquid metals to achieve a strong photothermal effect and their integration into thermoelectric devices with powerful light harvesting capabilities.

Intravascular Imaging of Atherosclerosis by Using Engineered Nanoparticles.

Atherosclerosis is a leading cause of morbidity and mortality, and high-risk atherosclerotic plaques can result in myocardial infarction, stroke, and/or sudden death. Various imaging and sensing techniques (e.g., ultrasound, optical coherence tomography, fluorescence, photoacoustic) have been developed for scanning inside blood vessels to provide accurate detection of high-risk atherosclerotic plaques. Nanoparticles have been utilized in intravascular imaging to enable targeted detection of high-risk plaques, to enhance image contrast, and in some applications to also provide therapeutic functions of atherosclerosis. In this paper, we review the recent progress on developing nanoparticles for intravascular imaging of atherosclerosis. We discuss the basic nanoparticle design principles, imaging modalities and instrumentations, and common targets for atherosclerosis. The review is concluded and highlighted with discussions on challenges and opportunities for bringing nanoparticles into in vivo (pre)clinical intravascular applications.

Molecularly targeted nanomedicine enabled by inorganic nanoparticles for atherosclerosis diagnosis and treatment.

Atherosclerosis, a chronic cardiovascular disease caused by plaque development in arteries, remains a leading cause of morbidity and mortality. Atherosclerotic plaques are characterized by the expression and regulation of key molecules such as cell surface receptors, cytokines, and signaling pathway proteins, potentially facilitating precise diagnosis and treatment on a molecular level by specifically targeting the characteristic molecules. In this review, we highlight the recent progress in the past five years on developing molecularly targeted nanomedicine for imaging detection and treatment of atherosclerosis with the use of inorganic nanoparticles. Through targeted delivery of imaging contrast nanoparticles to specific molecules in atherogenesis, atherosclerotic plaque development at different stages could be identified and monitored via various molecular imaging modalities. We also review molecularly targeted therapeutic approaches that target and regulate molecules associated with lipid regulation, inflammation, and apoptosis. The review is concluded with discussion on current challenges and future development of nanomedicine for atherosclerotic diagnosis and treatment.

A liquid metal-polydopamine composite for cell culture and electro-stimulation.

Gallium (Ga) is a low melting point metal in the liquid state in the biological environment which presents a unique combination of fluidity, softness, and metallic electrical and thermal properties. In this work, liquid Ga is proposed as a biocompatible electrode material for cell culture by electro-stimulation since the cytotoxicity of Ga is generally considered low and some Ga compounds have been reported to exhibit anti-bacterial and anti-inflammatory activities. Complementarily, polydopamine (PDA) was coated on liquid Ga to increase the attachment capability of cells on the liquid Ga electrode and provide enhanced biocompatibility. The liquid Ga layer could be readily painted at room temperature on a solid inert substrate, followed by the formation of a nanoscale PDA coating layer resulting in a conformable and biocompatible composite electrode. The PDA layer was shown to coordinate with Ga3+, which is sourced from liquid Ga, providing electrical conductivity in the cell culture medium. The PDA-Ga3+ composite acted as a conductive substrate for advanced electro-stimulation for cell culture methods of representative animal fibroblasts. The cell proliferation was observed to increase by ∼143% as compared to a standard glass coverslip at a low potential of 0.1 V of direct coupling stimulation. This novel PDA-Ga3+ composite has potential applications in cell culture and regenerative medicine.

Assembly of surface-independent polyphenol/liquid gallium composite nanocoatings.

The development of functional nanocoatings using natural compounds is a hallmark of sustainable strategies in the field of green synthesis. Herein, we report a surface-independent nanocoating strategy using natural polyphenols and gallium-based room temperature liquid metal nanoparticles. The nanocoating matrix is composed of tannic acid, crosslinked with group (IV) transition metal ions. Liquid gallium nanoparticles are incorporated into the coatings as a gallium ion releasing depot. The coating deposition is rapid and can be applied to a range of substrates including glass, plastics, paper, and metal surfaces, owing to the versatile adhesive nature of the catechol/gallol functional groups of tannic acid. The coating thickness can be controlled from 100 to 700 nm and the content of liquid gallium nanoparticles can be modulated. This enables the tunable release behaviour of gallium ions into the surrounding from the composite coatings. The coatings are highly biocompatible and display antioxidant and antibacterial properties that can be useful for diverse applications.

Low-temperature liquid platinum catalyst.

Insights into metal-matrix interactions in atomically dispersed catalytic systems are necessary to exploit the true catalytic activity of isolated metal atoms. Distinct from catalytic atoms spatially separated but immobile in a solid matrix, here we demonstrate that a trace amount of platinum naturally dissolved in liquid gallium can drive a range of catalytic reactions with enhanced kinetics at low temperature (318 to 343 K). Molecular simulations provide evidence that the platinum atoms remain in a liquid state in the gallium matrix without atomic segregation and activate the surrounding gallium atoms for catalysis. When used for electrochemical methanol oxidation, the surface platinum atoms in the gallium-platinum system exhibit an activity of [Formula: see text] three orders of magnitude higher than existing solid platinum catalysts. Such a liquid catalyst system, with a dynamic interface, sets a foundation for future exploration of high-throughput catalysis.

Nanoencapsulation for Probiotic Delivery.

Gut microbiota dynamically participate in diverse physiological activities with direct impact on the host's health. A range of factors associated with the highly complex intestinal flora ecosystem poses challenges in regulating the homeostasis of microbiota. The consumption of live probiotic bacteria, in principle, can address these challenges and confer health benefits. In this context, one of the major problems is ensuring the survival of probiotic cells when faced with physical and chemical assaults during their intake and subsequent gastrointestinal passage to the gut. Advances in the field have focused on improving conventional encapsulation techniques in the microscale to achieve high cell viability, gastric and temperature resistance, and longer shelf lives. However, these microencapsulation approaches are known to have limitations with possible difficulties in clinical translation. In this Perspective, we present a brief overview of the current progress of different probiotic encapsulation methods and highlight the contemporary and emerging single-cell encapsulation strategies using nanocoatings for individual probiotic cells. Finally, we discuss the relative advantages of various nanoencapsulation approaches and the future trend toward developing coated probiotics with advanced features and health benefits.

Exploring Interfacial Graphene Oxide Reduction by Liquid Metals: Application in Selective Biosensing.

Liquid metals (LMs) are electronic liquid with enigmatic interfacial chemistry and physics. These features make them promising materials for driving chemical reactions on their surfaces for designing nanoarchitectonic systems. Herein, we showed the interfacial interaction between eutectic gallium-indium (EGaIn) liquid metal and graphene oxide (GO) for the reduction of both substrate-based and free-standing GO. NanoIR surface mapping indicated the successful removal of carbonyl groups. Based on the gained knowledge, a composite consisting of assembled reduced GO sheets on LM microdroplets (LM-rGO) was developed. The LM enforced Ga3+ coordination within the rGO assembly found to modify the electrochemical interface for selective dopamine sensing by separating the peaks of interfering biologicals. Subsequently, paper-based electrodes were developed and modified with the LM-rGO that presented the compatibility of the assembly with low-cost commercial technologies. The observed interfacial interaction, imparted by LM's interfaces, and electrochemical performance observed for LM-rGO will lead to effective functional materials and electrode modifiers.

Nanotip Formation from Liquid Metals for Soft Electronic Junctions.

Liquid metals and alloys with high-aspect-ratio nanodimensional features are highly sought-after for emerging electronic applications. However, high surface tension, water-like fluidity, and the existence of self-limiting oxides confer specific peculiarities to their characteristics. Here, we introduce a high accuracy nanometric three-dimensional pulling and stretching method to fabricate liquid-metal-based nanotips from room- or near-room-temperature gallium-based alloys. The pulling rate and step size were controlled with a resolution of up to 10 nm and yielded different nanotip morphologies and lengths as a function of the base liquid metal alloy composition and the pulling parameters. The obtained nanotips presented high aspect ratios over lengths of a few microns and apexes between 10 and 100 nm. The liquid metal alloys were found confined within nanotips with about 10 nm apexes when vertically pulled at 100 nm/s. An amorphous gallium oxide skin was shown to cover the surface of the nanotips, while the liquid core was composed of the initial liquid metal alloys. The electrical contact established at the nanotips was characterized under dynamic conditions. The liquid metal nanotips showed an Ohmic resistance when a continuous liquid metal channel was formed, and a controllable semiconductor state corresponding to a heterojunction formed at the junction between the liquid metal phase and the gallium oxide semiconductor skin. The variable threshold voltages of the heterojunction were controlled via stretching of the nanotips with a 10 nm step resolution. The liquid metal nanotips were also used for establishing soft electronic junctions. This novel method of liquid metal nanotip fabrication with Ohmic and semiconducting behaviors will lead to exciting avenues for developing electronic and sensing devices.

Polydopamine Shell as a Ga3+ Reservoir for Triggering Gallium-Indium Phase Separation in Eutectic Gallium-Indium Nanoalloys.

Low melting point eutectic systems, such as the eutectic gallium-indium (EGaIn) alloy, offer great potential in the domain of nanometallurgy; however, many of their interfacial behaviors remain to be explored. Here, a compositional change of EGaIn nanoalloys triggered by polydopamine (PDA) coating is demonstrated. Incorporating PDA on the surface of EGaIn nanoalloys renders core-shell nanostructures that accompany Ga-In phase separation within the nanoalloys. The PDA shell keeps depleting the Ga3+ from the EGaIn nanoalloys when the synthesis proceeds, leading to a Ga3+-coordinated PDA coating and a smaller nanoalloy. During this process, the eutectic nanoalloys turn into non-eutectic systems that ultimately result in the solidification of In when Ga is fully depleted. The reaction of Ga3+-coordinated PDA-coated nanoalloys with nitrogen dioxide gas is presented as an example for demonstrating the functionality of such hybrid composites. The concept of phase-separating systems, with polymeric reservoirs, may lead to tailored materials and can be explored on a variety of post-transition metals.

Liquid metal dispersion by self-assembly of natural phenolics.

Gallic acid, a natural phenolic compound, efficiently establishes surface complexes with liquid gallium leading to the formation of an aqueous gallium dispersion via sonication. The surface functionalised gallium particles thus obtained were easily impregnated into paper membranes that could be turned from insulating to conductive by pressure induced deformation of the embedded particles.