Lubricant-entrenched slippery surface-based nanocarriers to avoid macrophage uptake and improve drug utilization.

INTRODUCTION: Reducing the protein adsorption of nanoparticles (NPs) as drug carriers to slow their rapid clearance by macrophages uptake is a critical challenge for NPs clinical translational applications. Despite extensive research efforts to inhibit cellular uptake, including covering biological agents or surface chemical coatings to impart "stealth" properties to NPs, their stability remains insufficient. OBJECTIVES: Developed a novel surface modification technology based on a physical infusion engineering approach to achieve persistent inhibition of protein adhesion and cellular uptake by nanocarriers. METHODS: The nanoparticles were prepared based on conventional drug carrier mesoporous silica NPs through a two-step process. A functional nanoscale slippery surface was formed by grafting "liquid-like" brushes on the particles surface, and then a lubricant-entrenched slippery surfaces (LESS) was formed by infusing silicone oil lubricant into the entire surface. Co-incubation with macrophages (in vitro and in vivo) was used to examine the anti-uptake properties of modified NPs. The anti-adhesion properties of LESS coating surfaces to various liquids, proteins and cells were used to analyze the anti-uptake mechanism. Loaded with drugs, combined with tumor models, to evaluate the drug utilization of modified NPs. RESULTS: Relying on the stable and slippery LESS coating, the modified surface could prevent the adhesion of various liquids and effectively shield against the adhesion of proteins and cells, as well as remarkably reduce macrophage cellular uptake in vitro and in vivo. In addition, the LESS coating does not affect cell activity and allows NPs to be loaded with drugs, significantly improving the utilization of drugs in vitro and in vivo. This allows the NPs to reach to the target tumor site for drug delivery without active clearance by macrophages. CONCLUSION: Our research introduces a new nanocarrier technology to improve anti-biofouling performance and stealth efficiency that will facilitate the development of nanomedicines for clinical transformation applications.

Anomalous dispersion of bioinspired flower-like microparticles for oil/water separation.

Hydrophobic particles have been suffering from aggregation in aqueous media, which limits their applications in oil/water separation. Surfactants have been used to increase the dispersity of the hydrophobic particles in water, but this approach compromises particles' hydrophobicity and oil absorption capabilities. Recently, hierarchical microparticles decorated with nanospikes were found to exhibit long-term anomalous dispersion in liquid medium without adding any surfactants. However, whether this anomalous dispersion phenomenon was applicable to 2D nano-petals decorated microparticles still remains unknown. Here, we developed a ZnO-based flower-like microparticles (FLMPs) whose surfaces were attached with 2D nano-petals, and we examined their anomalous dispersity. Our results showed that both hydrophilic and hydrophobic FLMPs could achieve anomalous dispersity either in water or organic solvents, likely due to reduced interparticle collision by the 2D nano-petals. In addition, the functional hydrophobic FLMPs also possessed a large surface area and superhydrophobic surfaces to efficiently absorb oil spills on water and oil emulsion suspended in water. In contrast, the hydrophobic microbeads (MBs) without nano-petals structure seriously aggregated in water and exhibited reduced oil absorption abilities. Our work demonstrated the new finding of 2D nano-pedal structure-mediated anomalous dispersity, and provided a new method for effective oil/water separation using superhydrophobic particles without surfactants.

Anti-biofouling NH3 gas sensor based on reentrant thorny ZnO/graphene hybrid nanowalls.

Since toxic gas leakage may cause ecological environmental problems and even life-threatening damage, effective monitoring of toxic gas is of great importance and subject to increasing demand. However, complicated environmental factors, as well as various coexisting interferences can easily affect the sensitivity and selectivity of gas sensors, hindering their performance. Recent reports have successfully demonstrated the development of hierarchical nanostructures with desirable self-cleaning properties, yet gas sensors that can resist contamination have rarely been realized. Here, we developed a reentrant thorny ZnO/graphene hybrid nanowall structure that simultaneously repels liquid contamination and possesses NH3 gas sensing properties. The unique reentrant and hierarchical structure, featuring an interconnected vertical graphene nanowall framework with numerous ZnO nanospikes branched on the top nanowall, is highly repellent to liquids, even biofluids with low surface tension. The hierarchical structure consisting of gas sensing graphene and ZnO can be successfully applied as an NH3 gas sensor at room temperature, exhibiting not only excellent sensitivity, selectivity, and repeatability, but also outstanding stability even after bacterial contamination. This study provides a versatile method for fabricating reentrant and hierarchical structures with excellent liquid repellency, and offers a promising method for designing reliable gas sensors with anti-biofouling properties.

Multifunctional Branched Nanostraw-Electroporation Platform for Intracellular Regulation and Monitoring of Circulating Tumor Cells.

Downstream analysis of circulating tumor cells (CTCs) has provided new insights into cancer research. In particular, the detection of CTCs, followed by the regulation and monitoring of their intracellular activities, can provide valuable information for comprehensively understanding cancer pathogenesis and progression. However, current CTC detection techniques are rarely capable of in situ regulation and monitoring of the intracellular microenvironments of cancer cells over time. Here, we developed a multifunctional branched nanostraw (BNS)-electroporation platform that could effectively capture CTCs and allow for downstream regulation and monitoring of their intracellular activities in a real-time and in situ manner. The BNSs possessed numerous nanobranches on the outer sidewall of hollow nanotubes, which could be conjugated with specific antibodies to facilitate the effective capture of CTCs. Nanoelectroporation could be applied through the BNSs to nondestructively porate the membranes of the captured cells at a low voltage, allowing the delivery of exogenous biomolecules into the cytosol and the extraction of cytosolic contents through the BNSs without affecting cell viability. The efficient delivery of biomolecules (e.g., small molecule dyes and DNA plasmids) into cancer cells with spatial and temporal control and, conversely, the repeated extraction of intracellular enzymes (e.g., caspase-3) for real-time monitoring were both demonstrated. This technology can provide new opportunities for the comprehensive understanding of cancer cell functions that will facilitate cancer diagnosis and treatment.

Reduced Graphene Oxide Nanohybrid-Assembled Microneedles as Mini-Invasive Electrodes for Real-Time Transdermal Biosensing.

A variety of nanomaterial-based biosensors have been developed to sensitively detect biomolecules in vitro, yet limited success has been achieved in real-time sensing in vivo. The application of microneedles (MN) may offer a solution for painless and minimally-invasive transdermal biosensing. However, integration of nanostructural materials on microneedle surface as transdermal electrodes remains challenging in applications. Here, a transdermal H2 O2 electrochemical biosensor based on MNs integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) is developed. The Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment. The Pt/rGO nanostructures are protected by a water-soluble polymer layer to avoid mechanical destruction during the MN skin insertion process. The polymer layer can readily be dissolved by the interstitial fluid and exposes the Pt/rGO on MNs for biosensing in vivo. The applications of the Pt/rGO-integrated MNs for in situ and real-time sensing of H2 O2 in vivo are demonstrated both on pigskin and living mice. This work offers a unique real-time transdermal biosensing system, which is a promising tool for sensing in vivo with high sensitivity but in a minimally-invasive manner.

Protection of Nanostructures-Integrated Microneedle Biosensor Using Dissolvable Polymer Coating.

Real-time transdermal biosensing provides a direct route to quantify biomarkers or physiological signals of local tissues. Although microneedles (MNs) present a mini-invasive transdermal technique, integration of MNs with advanced nanostructures to enhance sensing functionalities has rarely been achieved. This is largely due to the fact that nanostructures present on MNs surface could be easily destructed due to friction during skin insertion. In this work, we reported a dissolvable polymer-coating technique to protect nanostructures-integrated MNs from mechanical destruction during MNs insertion. After penetration into the skin, the polymer could readily dissolve by interstitial fluids so that the superficial nanostructures on MNs could be re-exposed for sensing purpose. To demonstrate this technique, metallic and resin MNs decorated with vertical ZnO nanowires (vNWs) were employed as an example. Dissolvable poly(vinyl pyrrolidone) was spray-coated on the vNW-MNs surface as a protective layer, which effectively protected the superficial ZnO NWs when MNs penetrated the skin. Transdermal biosensing of H2O2 biomarker in skin tissue using the polymer-protecting MNs sensor was demonstrated both ex vivo and in vivo. The results indicated that polymer coating successfully preserved the sensing functionalities of the MNs sensor after inserting into the skin, whereas the sensitivity of the MN sensor without a coating protection was significantly compromised by 3-folds. This work provided unique opportunities of protecting functional nanomodulus on MNs surface for minimally invasive transdermal biosensing.

Physical activation of innate immunity by spiky particles.

Microbial biochemicals have been indicated as the primary stimulators of innate immunity, the first line of the body's defence against infections. However, the influence of topological features on a microbe's surface on immune responses remains largely unknown. Here we demonstrate the ability of TiO2 microparticles decorated with nanospikes (spiky particles) to activate and amplify the immune response in vitro and in vivo. The nanospikes exert mechanical stress on the cells, which results in potassium efflux and inflammasome activation in macrophages and dendritic cells during phagocytosis. The spiky particles augment antigen-specific humoral and cellular immune responses in the presence of monophosphoryl lipid A and elicit protective immunity against tumour growth and influenza viral infection. The study offers insights into how surface physical cues can tune the activation of innate immunity and provides a basis for engineering particles with increased immunogenicity and adjuvanticity.

Nanospikes-mediated Anomalous Dispersities of Hydropobic Micro-objects and their Application for Oil Emulsion Cleaning.

Many fields of applications require dispersion of hydrophobic particles in water, which is traditionally achieved by using surfactants or amphiphilic molecules to modify particle surfaces. However, surfactants or amphiphilic molecules may disturb the native solution or particles' surface hydrophobicity, limiting extended applications such as oil emulsion cleaning. Recently one example of 2 µm-size polystyrene microparticles covered with ZnO nanospikes has been shown to exhibit excellent dispersity in water in spite of surface hydrophobicity. Whether this anomalous dispersion phenomenon was applicable to other hydrophobic microparticle systems was still unclear and its application scope was limited. Here the anomalous dispersities of different hydrophobic spiky micro-objects were systematically explored. The results show that the anomalous dispersion phenomenon was universally observed on different hydrophobic spiky micro-objects including different hydrophobic coating, particle sizes, material compositions and core particle morphologies. In addition, the spiky micro-objects displayed anomalous dispersity in water without compromising surface hydrophobicity, and their applications for oil spills absorption and oil emulsion cleaning were demonstrated. This work offers unique insight on the nanospikes-mediated anomalous dispersion phenomenon of hydrophobic micro-object and potentially extends its applicability and application scopes.

Anomalous dispersion of magnetic spiky particles for enhanced oil emulsions/water separation.

In situ effective separation of oil pollutants including oil spills and oil emulsions from water is an emerging technology yet remains challenging. Hydrophobic micro- or nano-materials with ferromagnetism have been explored for oil removal, yet the separation efficiency of an oil emulsion was compromised due to the limited dispersion of hydrophobic materials in water. A surfactant coating on microparticles prevented particle aggregation, but reduced oil absorption and emulsion cleaning ability. Recently, polystyrene microbeads covered with nanospikes have been reported to display anomalous dispersion in phobic media without surfactants. Inspired by this phenomenon, here magnetic microparticles attached with nanospikes were fabricated for enhanced separation of oil emulsions from water. In this design, the particle surfaces were functionalized to be superhydrophobic/superoleophilic for oil absorption, while the surface of the nanospikes prevented particle aggregation in water without compromising surface hydrophobicity. The magnetic spiky particles effectively absorbed oil spills on the water surface, and readily dispersed in water and offered facile cleaning of the oil emulsion. In contrast, hydrophobic microparticles without nanospikes aggregated in water limiting the particle-oil contact, while surfactant coating severely reduced particle hydrophobicity and oil absorption ability. Our work provides a unique application scope for the anomalous dispersity of microparticles and their potential opportunities in effective oil-water separation.

A fluorescence enhancement probe based on BODIPY for the discrimination of cysteine from homocysteine and glutathione.

Herein, a fluorescent probe BODIPY-based glyoxal hydrazone (BODIPY-GH) (1) for cysteine based on inhibiting of intramolecular charge transfer (ICT) quenching process upon reaction with the unsaturated aldehyde has been synthesized, which exhibits longer excitation wavelength, selective and sensitive colorimetric and fluorimetric response toward cysteine in natural media. The probe shows highly selectivity towards cysteine over homocysteine and glutathione as well as other amino acids with a significant fluorescence enhancement response within 15min In the presence of 50 equiv. of homocysteine, the emission increased slightly within 15min and completed in 2.5h to reach its maximum intensity. Therefore, the discrimination of cysteine from homocysteine and glutathione can be achieved through detection of probe 1. It shows low cytotoxicity and excellent membrane permeability toward living cells, which was successfully applied to detect and image intracellular cysteine effectively by confocal fluorescence imaging.

Fluorescent glutathione probe based on MnO2-phenol formaldehyde resin nanocomposite.

MnO2-phenol formaldehyde resin (MnO2-PFR) nanocomposite is successfully prepared by a simple chemical reduction process. The resultant MnO2-PFR nanocomposite is well characterized. The absorption band of non-fluorescent MnO2 nanosheets overlaps well with the fluorescence emission of PFR nanoparticles. The green fluorescence of PFR in this nanocomposite can be effectively quenched by fluorescence resonance energy transfer from PFR to MnO2. In the presence of glutathione (GSH), the fluorescence of PFR could be recovered due to MnO2 was reduced to Mn(2+) by GSH. The nanocomposite can be use for detecting glutathione in blood serum.