Self-assembled and pH-responsive polymeric nanomicelles impart effective delivery of paclitaxel to cancer cells.

Chemotherapy is an essential component of breast cancer therapy, but it is associated with serious side effects. Herein, a pluronic F68-based pH-responsive, and self-assembled nanomicelle system was designed to improve the delivery of paclitaxel (PTX) to breast cancer cells. Two pH-responsive pluronic F68-PTX conjugates succinoyl-linked conjugate (F68-SA-PTX) and -aconityl-linked conjugate (F68-CAA-PTX) were designed to respond the varying pH-environment in tumour tissue.

Acoustofection: High-Frequency Vibrational Membrane Permeabilization for Intracellular siRNA Delivery into Nonadherent Cells.

The internalization of therapeutic molecules into cells-a critical step in enabling a suite of autologous ex vivo gene and cell therapies-is highly regulated by the lipid barrier imposed by the cell membrane. Strategies to increase the efficiency of delivering these exogenous payloads into the cell, while maintaining the integrity of both the therapeutic molecules to be delivered as well as the host cells they are delivered to, are therefore required. This is especially the case for suspension cells that are particularly difficult to transfect.

High Frequency Sonoprocessing: A New Field of Cavitation-Free Acoustic Materials Synthesis, Processing, and Manipulation.

Ultrasound constitutes a powerful means for materials processing. Similarly, a new field has emerged demonstrating the possibility for harnessing sound energy sources at considerably higher frequencies (10 MHz to 1 GHz) compared to conventional ultrasound (⩽3 MHz) for synthesizing and manipulating a variety of bulk, nanoscale, and biological materials. At these frequencies and the typical acoustic intensities employed, cavitation-which underpins most sonochemical or, more broadly, ultrasound-mediated processes-is largely absent, suggesting that altogether fundamentally different mechanisms are at play.

High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium-dependent mechanism.

Exosomes are promising disease diagnostic markers and drug delivery vehicles, although their use in practice is limited by insufficient homogeneous quantities that can be produced. We reveal that exposing cells to high frequency acoustic irradiation stimulates their generation without detriment to cell viability by exploiting their innate membrane repair mechanism, wherein the enhanced recruitment of calcium ions from the extracellular milieu into the cells triggers an ESCRT pathway known to orchestrate exosomal production. Given the high post-irradiation cell viabilities (≈95%), we are able to recycle the cells through iterative irradiation and post-excitation incubation steps, which facilitate high throughput production of a homogeneous population of exosomes-a particular challenge for translating exosome therapy into clinical practice.

Antitumor and Antiangiogenic Properties of Gold(III) Complexes Containing Cycloaurated Triphenylphosphine Sulfide Ligands.

A family of stable anticancer gold(III)-based therapeutic complexes containing cyclometalated triphenylphosphine sulfide ligands have been prepared. The anticancer properties of the newly developed complexes [AuCl{κ-2-CHP(S)Ph}] (), [Au(κ-SCNEt){κ-2-CHP(S)Ph}]PF (), [AuCl(dppe){κ-2-CHP(S)Ph}]Cl (), and [Au(dppe){κ-2-CHP(S)Ph}][PF] () were investigated toward five human cancer cell lines [cervical (HeLa), lung (A549), prostate (PC3), fibrosarcoma (HT1080), and breast (MDA-MB-231)]. cytotoxicity studies revealed that compounds - displayed potent cell growth inhibition (IC values in the range of 0.

On-Chip Generation of Vortical Flows for Microfluidic Centrifugation.

Microcentrifugation constitutes an important part of the microfluidic toolkit in a similar way that centrifugation is crucial to many macroscopic procedures, given that micromixing, sample preconcentration, particle separation, component fractionation, and cell agglomeration are essential operations in small scale processes. Yet, the dominance of capillary and viscous effects, which typically tend to retard flow, over inertial and gravitational forces, which are often useful for actuating flows and hence centrifugation, at microscopic scales makes it difficult to generate rotational flows at these dimensions, let alone with sufficient vorticity to support efficient mixing, separation, concentration, or aggregation. Herein, the various technologies-both passive and active-that have been developed to date for vortex generation in microfluidic devices are reviewed.

Potent and Selective Cytotoxic and Anti-inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands.

Four cycloaurated phosphine sulfide complexes, [Au{κ -2-C H P(S)Ph } ][AuX ] [X=Cl (2), Br (3), I (4)] and [Au{κ -2-C H P(S)Ph } ]PF (5), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological-like conditions and showed excellent cytotoxicity against a broad range of cancer cell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer (HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductase and induction of apoptosis through mitochondrial disruption.

Acoustopipetting: Tunable Nanoliter Sample Dispensing Using Surface Acoustic Waves.

We seek to demonstrate a robust, low-cost, and user-friendly acoustomicrofluidic platform that facilitates rapid, reproducible, and precise nanoliter sample dispensing. The solid-state chipscale platform exploits the unprecedented acceleration arising from high-frequency nanoelectromechanical vibrations, on the order of 10 million g, to jet the sample and hence generate a liquid bridge that spans across the substrate, on which the vibrations are generated and from which the sample originates, to a top target plate before rapidly pinching off to deposit the sample on the target with precise and reproducible volumes that can be tuned down to 0.22 μL with a standard error of 6.

High frequency acoustic permeabilisation of drugs through tissue for localised mucosal delivery.

The majority of infectious diseases enter the body through mucosal membranes that line the ocular, nasal, oral, vaginal and rectal surfaces. As infections can be effectively prevented by instigating a local immune response in the immunocyte-rich regions of the mucosa, an efficacious route of vaccine administration is to directly target their delivery to these surfaces. It is nevertheless challenging to provide sufficient driving force to penetrate both the mucus lining as well as the epithelial barrier of the mucosal surfaces, which are designed to effectively keep foreign entities out, but not excessively such that the therapeutic agent penetrates deeper into the vascularised submucosal regions where they are mostly taken up by the systemic circulation, thus resulting in a far weaker immune response.

Acoustically-mediated intracellular delivery.

Recent breakthroughs in gene editing have necessitated practical ex vivo methods to rapidly and efficiently re-engineer patient-harvested cells. Many physical membrane-disruption or pore-forming techniques for intracellular delivery, however, result in poor cell viability, while most carrier-mediated techniques suffer from suboptimal endosomal escape and hence cytoplasmic or nuclear targeting. In this work, we show that short exposure of cells to high frequency (>10 MHz) acoustic excitation facilitates temporal reorganisation of the lipid structure in the cell membrane that enhances translocation of gold nanoparticles and therapeutic molecules into the cell within just ten minutes.

Correction: Continuous tuneable droplet ejection via pulsed surface acoustic wave jetting.

Correction for 'Continuous tuneable droplet ejection via pulsed surface acoustic wave jetting' by Jasmine O. Castro et al., Soft Matter, 2018, DOI: 10.

Continuous tuneable droplet ejection via pulsed surface acoustic wave jetting.

We report a miniaturised platform for continuous production of single or multiple liquid droplets with diameters between 60 and 500 μm by interfacing a capillary-driven self-replenishing liquid feed with pulsed excitation of focussed surface acoustic waves (SAWs). The orifice-free operation circumvents the disadvantages of conventional jetting systems, which are often prone to clogging that eventuates in rapid degradation of the operational performance. Additionally, we show the possibility for flexibly tuning the ejected droplet size through the pulse width duration, thus avoiding the need for a separate device for every different droplet size required, as is the case for systems in which the droplet size is set by nozzles and orifices, as well as preceding ultrasonic jetting platforms where the droplet size is controlled by the operating frequency.

Plug-and-actuate on demand: multimodal individual addressability of microarray plates using modular hybrid acoustic wave technology.

The microarray titre plate remains a fundamental workhorse in genomic, proteomic and cellomic analyses that underpin the drug discovery process. Nevertheless, liquid handling technologies for sample dispensing, processing and transfer have not progressed significantly beyond conventional robotic micropipetting techniques, which are not only at their fundamental sample size limit, but are also prone to mechanical failure and contamination. This is because alternative technologies to date suffer from a number of constraints, mainly their limitation to carry out only a single liquid operation such as dispensing or mixing at a given time, and their inability to address individual wells, particularly at high throughput.

Acoustically-driven thread-based tuneable gradient generators.

Thread-based microfluidics offer a simple, easy to use, low-cost, disposable and biodegradable alternative to conventional microfluidic systems. While it has recently been shown that such thread networks facilitate manipulation of fluid samples including mixing, flow splitting and the formation of concentration gradients, the passive capillary transport of fluid through the thread does not allow for precise control due to the random orientation of cellulose fibres that make up the thread, nor does it permit dynamic manipulation of the flow. Here, we demonstrate the use of high frequency sound waves driven from a chip-scale device that drives rapid, precise and uniform convective transport through the thread network.

Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments.

The experimental systems that recapitulate the complexity of native tissues and enable precise control over the microenvironment are becoming essential for the pre-clinical tests of therapeutics and tissue engineering. Here, we described a strategy to develop an in vitro platform to study the developmental biology of craniofacial osteogenesis. In this study, we directly osteo-differentiated cranial neural crest cells (CNCCs) in a 3-D in vitro bioengineered microenvironment.