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.

Functionalized Spiky Particles for Intracellular Biomolecular Delivery.

The intracellular delivery of biomolecules is of significant importance yet challenging. In addition to the conventional delivery of nanomaterials that rely on biochemical pathways, vertical nanowires have been recently proposed to physically penetrate the cell membrane, thus enabling the direct release of biomolecules into the cytoplasm circumventing endosomal routes. However, due to the inherent attachment of the nanowires to a planar 2D substrate, nanowire cell penetrations are restricted to in vitro applications, and they are incapable of providing solution-based delivery. To overcome this structural limitation, we created polyethylenimine-functionalized microparticles covered with nanospikes, namely, "spiky particles", to deliver biomolecules by utilizing the nanospikes to penetrate the cell membrane. The nanospikes might penetrate the cell membrane during particle engulfment, and this enables the bound biomolecules to be released directly into the cytosol. TiO2 spiky particles were fabricated through hydrothermal routes, and they were demonstrated to be biocompatible with HeLa cells, macrophage-like RAW cells, and fibroblast-like 3T3-L1 cells. The polyethylenimine-functionalized spiky particles provided direct delivery of fluorescent siRNA into cell cytosol and functional siRNA for gene knockdown as well as successful DNA plasmid transfection which were difficult to achieve by using microparticles without nanospikes. The spiky particles presented a unique direct cell membrane penetrant vehicle to introduce biomolecules into cell cytosol, where the biomolecules might bypass conventional endocytic degradation routes.

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.

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.

Transdermal Delivery of Living and Biofunctional Probiotics through Dissolvable Microneedle Patches.

Bioactive functional probiotics play an important role in many health applications such as maintaining skin health and the immunity of the human host. Artificial supplementation of probiotics would enhance immune functions as well as regulate skin health. However, simple and effective methods to deliver probiotics into the dermis to regulate local dermal tissue are still lacking. Furthermore, microneedles have been used for transdermal drug delivery in a pain-free manner, yet there were few reported methods to deliver living microbes via microneedles. In this work, we developed a technique to deliver bioactive functional probiotics, using lactobacillus as the model probiotic, into local dermis by dissolvable microneedles. The transdermal delivery of probiotics might enhance local skin regulation and immunity, and dissolvable microneedles served as a safe and pain-free tool for dermal microbial delivery. Lactobacillus was encapsulated in dissolvable microneedles with high viability by a centrifugation casting method. The microneedles rapidly dissolved after skin penetration, releasing the lactobacillus into the subcutaneous space, without causing local tissue irritation. The lactobacillus was functionally bioactive following transdermal delivery, actively synthesizing lactic acid both ex vivo and in vivo. Our technique provided a safe, effective, and convenient approach for the transdermal delivery of probiotics into local skin, with the potential to improve skin health and immunity.