Tailored Fluorosurfactants through Controlled/Living Radical Polymerization for Highly Stable Microfluidic Droplet Generation.

Droplet-based microfluidics represents a disruptive technology in the field of chemistry and biology through the generation and manipulation of sub-microlitre droplets. To avoid droplet coalescence, fluoropolymer-based surfactants are commonly used to reduce the interfacial tension between two immiscible phases to stabilize droplet interfaces. However, the conventional preparation of fluorosurfactants involves multiple steps of conjugation reactions between fluorinated and hydrophilic segments to form multiple-block copolymers. In addition, synthesis of customized surfactants with tailored properties is challenging due to the complex synthesis process. Here, we report a highly efficient synthetic method that utilizes living radical polymerization (LRP) to produce fluorosurfactants with tailored functionalities. Compared to the commercialized surfactant, our surfactants outperform in thermal cycling for polymerase chain reaction (PCR) testing, and exhibit exceptional biocompatibility for cell and yeast culturing in a double-emulsion system. This breakthrough synthetic approach has the potential to revolutionize the field of droplet-based microfluidics by enabling the development of novel designs that generate droplets with superior stability and functionality for a wide range of applications.

Vector enabled CRISPR gene editing - A revolutionary strategy for targeting the diversity of brain pathologies.

Brain pathologies are considered one of the greatest contributors of death and disability worldwide. Neurodegenerative Alzheimer's disease is the second leading cause of death in adults, whilst brain cancers including glioblastoma multiforme in adults, and pediatric-type high-grade gliomas in children remain largely untreatable. A further compounding issue for patients with brain pathologies is that of long-term neuropsychiatric sequela - as a symptom or arising from high dose therapeutic intervention. The major challenge to effective, low dose treatment is finding therapeutics that successfully cross the blood-brain barrier and target aberrant cellular processes, while having minimum effect on essential cellular processes, and healthy bystander cells. Following over 30 years of research, CRISPR technology has emerged as a biomedical tour de force with the potential to revolutionise the treatment of both neurological and cancer related brain pathologies. The aim of this review is to take stock of the progress made in CRISPR technology in relation to treating brain pathologies. Specifically, we will describe studies which look beyond design, synthesis, and theoretical application; and focus instead on in vivo studies with translation potential. Along with discussing the latest breakthrough techniques being applied within the CRISPR field, we aim to provide a prospective on the knowledge gaps that exist and challenges that still lay ahead for CRISPR technology prior to successful application in the brain disease treatment field.

Low-Fouling Gold Nanorod Theranostic Agents Enabled by a Sulfoxide Polymer Coating.

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and in vivo circulation time of the GNRs and compared these properties with pegylated GNR counterparts. The photothermal effect and photoacoustic imaging of these polymer-coated GNRs were also explored, and the results show that these GNRs are promising as nanotheranostic particles for the treatment of cancer.

Antifouling Surfaces Enabled by Surface Grafting of Highly Hydrophilic Sulfoxide Polymer Brushes.

Antifouling surfaces are important in a broad range of applications. An effective approach to antifouling surfaces is to covalently attach antifouling polymer brushes. This work reports the synthesis of a new class of antifouling polymer brushes based on highly hydrophilic sulfoxide polymers by surface-initiated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The sulfoxide polymer brushes are able to effectively reduce nonspecific adsorption of proteins and cells, demonstrating remarkable antifouling properties. Given the outstanding antifouling behavior of the sulfoxide polymers and versatility of surface-initiated PET-RAFT technology, this work presents a useful and general approach to engineering various material surfaces with antifouling properties, for potential biomedical applications in areas such as tissue engineering, medical implants, and regenerative medicine.

Photo-Degradable Micelles Capable of Releasing of Carbon Monoxide under Visible Light Irradiation.

Carbon monoxide (CO) has emerged as a potential therapeutic agent for the treatment of many diseases. However, the therapeutic outcome is highly dependent on the dosages and administration sites. Hence, there is mounting interest in the development of CO-releasing materials to accomplish site-specific and dose-controlled delivery of CO. Herein, a micellar nanoparticle platform for the photo-mediated release of CO by using amphiphilic triblock copolymers bearing CO-releasing moieties of 3-hydroxylflavone (3-HF) derivatives within the middle blocks is developed. These micelles are relatively stable without CO leakage but undergo visible light-mediated CO release and simultaneous main chain scission. Moreover, these micellar nanoparticles are cytocompatible regardless of light irradiation, which shows unique anti-inflammatory performance only after light irradiation as a result of photo-triggered CO release. This work may represent the first example of main-chain degradable micellar nanocarriers with controlled CO-releasing performance for potential anti-inflammatory applications.

Engineering Organic/Inorganic Nanohybrids through RAFT Polymerization for Biomedical Applications.

Despite many early accomplishments in nanomaterial design and synthesis, there remains a significant requirement for novel inorganic and organic nanohybrids with the potential to act as efficacious molecular imaging agents and theranostic vectors. The functionalization of surfactant-coated inorganic nanoparticles with polymer shells represents one of the most suitable and popular methods to synthesize polymer/inorganic nanohybrids for theranostic applications. Key requirements for effective imaging agent design include water dispersibility, biocompatibility and functionality to enable enhanced contrast magnetic resonance imaging (MRI), positron-emission tomography (PET), computed tomography (CT), or ultrasound modalities. In this Perspective, we highlight recent advances in the fabrication of organic/inorganic nanohybrids exploiting functionalized polymers prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer shells can imbue favorable traits to the nanoparticles such as stealth, image enhancement, storage (and release) of therapeutics, and sensitivity to biological stimuli. In this Perspective, we discuss the design and synthesis of hybrid nanoparticles and discuss current trends and future opportunities.

Electrospun Nanofibrous Cellulose Acetate/Curcumin Membranes for Fast Detection of Pb Ions.

Fast detection of Pb2+ pollution has become an important issue in the environment field and food industry. In this work, electrospun nanofibrous cellulose acetate/curcumin membranes (ENCACMs) and pure cellulose acetate (CA) membranes were fabricated by the electrospinning technique. Then the fast detection of heavy metals by these membranes was observed by naked eyes and digital camera. Fabricated ENCACMs showed obvious selectivity to the Pb2+ at pH 9. Pb2+ detection sensitivity of ENCACMs with a thickness of 0.2 mm was 1 mM (limit of detection) at pH 9. The sensitivity depended on the pH of solution and membrane thickness. However, it was not incubation time dependent. This work provides a simple, cheap, and fast method for detecting Pb2+. Moreover, this method is environmentally friendly to the detection solution and is simply post-treated after the detection process.

Soybean Lecithin-Mediated Nanoporous PLGA Microspheres with Highly Entrapped and Controlled Released BMP-2 as a Stem Cell Platform.

Injectable polymer microsphere-based stem cell delivery systems have a severe problem that they do not offer a desirable environment for stem cell adhesion, proliferation, and differentiation because it is difficult to entrap a large number of hydrophilic functional protein molecules into the core of hydrophobic polymer microspheres. In this work, soybean lecithin (SL) is applied to entrap hydrophilic bone morphogenic protein-2 (BMP-2) into nanoporous poly(lactide-co-glycolide) (PLGA)-based microspheres by a two-step method: SL/BMP-2 complexes preparation and PLGA/SL/BMP-2 microsphere preparation. The measurements of their physicochemical properties show that PLGA/SL/BMP-2 microspheres had significantly higher BMP-2 entrapment efficiency and controlled triphasic BMP-2 release behavior compared with PLGA/BMP-2 microspheres. Furthermore, the in vitro and in vivo stem cell behaviors on PLGA/SL/BMP-2 microspheres are analyzed. Compared with PLGA/BMP-2 microspheres, PLGA/SL/BMP-2 microspheres have significantly higher in vitro and in vivo stem cell attachment, proliferation, differentiation, and matrix mineralization abilities. Therefore, injectable nanoporous PLGA/SL/BMP-2 microspheres can be potentially used as a stem cell platform for bone tissue regeneration. In addition, SL can be potentially used to prepare hydrophilic protein-loaded hydrophobic polymer microspheres with highly entrapped and controlled release of proteins.

Microfluidic Mass Production of Stabilized and Stealthy Liquid Metal Nanoparticles.

Functional nanoparticles comprised of liquid metals, such as eutectic gallium indium (EGaIn) and Galinstan, present exciting opportunities in the fields of flexible electronics, sensors, catalysts, and drug delivery systems. Methods used currently for producing liquid metal nanoparticles have significant disadvantages as they rely on both bulky and expensive high-power sonication probe systems, and also generally require the use of small molecules bearing thiol groups to stabilize the nanoparticles. Herein, an innovative microfluidics-enabled platform is described as an inexpensive, easily accessible method for the on-chip mass production of EGaIn nanoparticles with tunable size distributions in an aqueous medium. A novel nanoparticle-stabilization approach is reported using brushed polyethylene glycol chains with trithiocarbonate end-groups negating the requirements for thiol additives while imparting a "stealth" surface layer. Furthermore, a surface modification of the nanoparticles is demonstrated using galvanic replacement and conjugation with antibodies. It is envisioned that the demonstrated microfluidic technique can be used as an economic and versatile platform for the rapid production of liquid metal-based nanoparticles for a range of biomedical applications.

Bioconjugation and Fluorescence Labeling of Iron Oxide Nanoparticles Grafted with Bromomaleimide-Terminal Polymers.

Iron oxide nanoparticles have been widely applied in biomedical applications for their unique physical properties. Despite the relatively mature synthetic approaches for iron oxide nanoparticles, surface modification strategies for obtaining particles with satisfactory biofunctionality are still urgently needed to meet the challenge of nanomedicine. Herein, we report a surface modification and biofunctionalization strategy for iron oxide-based magnetic nanoparticles based on a dibromomaleimide (DBM)-terminated polymer with brushed polyethylene glycol (PEG) chains. PEG acrylate and phosphonate monomers, serving as antibiofouling and surface anchoring compartments for iron oxide nanoparticles, were incorporated utilizing a novel DBM containing reversible addition-fragmentation chain transfer (RAFT) agent. The particles prepared through this new surface architecture possessed high colloidal stability in a physiological buffer and the capacity of covalent conjugation with biomolecules for targeting. Cell tracking of the molecular probes was achieved concomitantly by exploiting DBM conjugation-induced fluorescence of the nanoparticles.

Recent Advances of Electrospun Nanofibrous Membranes in the Development of Chemosensors for Heavy Metal Detection.

It is critical to detect and analyze the heavy metal pollutions in environments and foods. Chemosensors have been widely investigated for fast detection of analytes such as heavy metals due to their unique advantages. In order to improve the detection sensitivity of chemosensors, recently electrospun nanofibrous membranes (ENMs) have been explored for the immobilization of chemosensors or receptors due to their high surface-to-volume ratio, high porosity, easiness of fabrication and functionalization, controllability of nanofiber properties, low cost, easy detection, no obvious pollution to the detection solution, and easy post-treatment after the detection process. The purpose of this review is to summarize and guide the development and application of ENMs in the field of chemosensors for the detection of analytes, especially heavy metals. First, heavy metals, chemosensors, and four types of preparation methods for ENM-immobilized chemosensors/receptors are briefly introduced. And then, ENM-immobilized chemosensors/receptors and their application progresses for optical, electro, and mass detections of heavy metals are reviewed according to the four types of preparation methods. Finally, the application of ENM-immobilized chemosensors/receptors is summarized and an outlook is provided. The review will provide an instruction to the research and development of ENM-immobilized chemosensors/receptors for the detection of analytes.

Strategies to overcome the barrier: use of nanoparticles as carriers and modulators of barrier properties.

The blood-brain barrier (BBB) protects the brain from toxic substances within the bloodstream and keeps the brain's homeostasis stable. On the other hand, it also represents the main obstacle in the treatment of many CNS diseases. Among different techniques, nanoparticles have emerged as promising tools to enhance brain drug delivery of therapeutic molecules. For successful drug delivery, nanoparticles may either modulate BBB integrity or exploit transport systems present on the endothelium. In this review, we present two different nanoparticles to enhance brain drug delivery. Poly(butyl cyanoacrylate) nanoparticles were shown to induce a reversible disruption of the BBB in vitro which may be exploited by simultaneous injection of the drug in question. By coating the poly(butyl cyanoacrylate) nanoparticles with, e.g., ApoE, it is also possible to circumvent the BBB via the LDL-receptor. Another example of the use of receptor-mediated endocytosis to enhance brain uptake of nanoparticles are poly(ethylene glycol)-coated Fe3O4 nanoparticles which are covalently attached to lactoferrin. These nanoparticles have been shown to facilitate the transport via the lactoferrin receptor, and so could then be used for magnetic resonance imaging.

Advancing Tissue Culture with Light-Driven 3D-Printed Microfluidic Devices.

Three-dimensional (3D) printing presents a compelling alternative for fabricating microfluidic devices, circumventing certain limitations associated with traditional soft lithography methods. Microfluidics play a crucial role in the biomedical sciences, particularly in the creation of tissue spheroids and pharmaceutical research. Among the various 3D printing techniques, light-driven methods such as stereolithography (SLA), digital light processing (DLP), and photopolymer inkjet printing have gained prominence in microfluidics due to their rapid prototyping capabilities, high-resolution printing, and low processing temperatures. This review offers a comprehensive overview of light-driven 3D printing techniques used in the fabrication of advanced microfluidic devices. It explores biomedical applications for 3D-printed microfluidics and provides insights into their potential impact and functionality within the biomedical field. We further summarize three light-driven 3D printing strategies for producing biomedical microfluidic systems: direct construction of microfluidic devices for cell culture, PDMS-based microfluidic devices for tissue engineering, and a modular SLA-printed microfluidic chip to co-culture and monitor cells.

Fluorine-modified polymers reduce the adsorption of immune-reactive proteins to PEGylated gold nanoparticles.

Aim: To investigate the influence of fluorine in reducing the adsorption of immune-reactive proteins onto PEGylated gold nanoparticles. Methods: Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare polymer-coated gold nanoparticles. Subsequent in vitro physicochemical and biological characterizations and proteomic analysis were performed. Results: Fluorine-modified polymers reduced the adsorption of complement and other immune-reactive proteins while potentially improving circulatory times and modulating liver toxicity by reducing apolipoprotein E adsorption. Fluorine actively discouraged phagocytosis while encouraging the adsorption of therapeutic targets, CD209 and signaling molecule calreticulin. Conclusion: This study suggests that the addition of fluorine in the surface coating of nanoparticles could lead to improved performance in nanomedicine designed for the intravenous delivery of cargos.

Nanomedicines are based around the delivery of therapies by tiny, nanosized delivery vehicles. This method offers a much better way of specifically targeting life-threatening diseases. For fast delivery, nanomedicines can be injected into the blood (intravenously); however, this often leads to an unwanted and exaggerated immune response. The immune system is activated by proteins in the blood that attach themselves to nanoparticles through various chemical interactions (the protein corona effect). Fluorine is a chemical routinely used in surfactants such as firefighting foam and more recently in molecular imaging and nanoparticles designed for the delivery of therapies aimed at cancer. While fluorine has great potential to improve the cellular uptake of therapies, little is known about whether it can also help camouflage the nanoparticles against the immune system responses. Here, using fluorinated polymer-coated gold nanoparticles, the authors demonstrate that fluorine reduces uptake by immune cells and is highly effective at reducing the binding of immune system-initiating proteins. This work successfully illustrates the rationale for more widespread investigation of fluorine during the development of polymer-coated nanoparticles designed for the intravenous delivery of nanomedicines.

Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma.

Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood-brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) - as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity - meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment-focused MRI-siRNA theranostics for the better treatment and diagnosis of medulloblastoma.

3D-printed liquid metal polymer composites as NIR-responsive 4D printing soft robot.

4D printing combines 3D printing with nanomaterials to create shape-morphing materials that exhibit stimuli-responsive functionalities. In this study, reversible addition-fragmentation chain transfer polymerization agents grafted onto liquid metal nanoparticles are successfully employed in ultraviolet light-mediated stereolithographic 3D printing and near-infrared light-responsive 4D printing. Spherical liquid metal nanoparticles are directly prepared in 3D-printed resins via a one-pot approach, providing a simple and efficient strategy for fabricating liquid metal-polymer composites. Unlike rigid nanoparticles, the soft and liquid nature of nanoparticles reduces glass transition temperature, tensile stress, and modulus of 3D-printed materials. This approach enables the photothermal-induced 4D printing of composites, as demonstrated by the programmed shape memory of 3D-printed composites rapidly recovering to their original shape in 60 s under light irradiation. This work provides a perspective on the use of liquid metal-polymer composites in 4D printing, showcasing their potential for application in the field of soft robots.

Magnetic iron oxide nanoparticles for brain imaging and drug delivery.

Central nervous system (CNS) disorders affect as many as 1.5 billion people globally. The limited delivery of most imaging and therapeutic agents into the brain is a major challenge for treatment of CNS disorders. With the advent of nanotechnologies, controlled delivery of drugs with nanoparticles holds great promise in CNS disorders for overcoming the blood-brain barrier (BBB) and improving delivery efficacy. In recent years, magnetic iron oxide nanoparticles (MIONPs) have stood out as a promising theranostic nanoplatform for brain imaging and drug delivery as they possess unique physical properties and biodegradable characteristics. In this review, we summarize the recent advances in MIONP-based platforms as imaging and drug delivery agents for brain diseases. We firstly introduce the methods of synthesis and surface functionalization of MIONPs with emphasis on the inclusion of biocompatible polymers that allow for the addition of tailored physicochemical properties. We then discuss the recent advances in in vivo imaging and drug delivery applications using MIONPs. Finally, we present a perspective on the remaining challenges and possible future directions for MIONP-based brain delivery systems.

Connecting liquid metals with sound.

A stretchable conductive circuit is formed using a liquid metal-polymer composite.

Keeping up with the COVID's-Could siRNA-based antivirals be a part of the answer?

Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This deadly infection has resulted in more than 5.2 million deaths worldwide. The global rollout of COVID-19 vaccines has without doubt saved countless lives by reducing the severity of symptoms for patients. However, as the virus continues to evolve, there is a risk that the vaccines and antiviral designed to target the infection will no longer be therapeutically viable. Furthermore, there remain fears over both the short and long-term side effects of repeat exposure to currently available vaccines. In this review, we discuss the pros and cons of the vaccine rollout and promote the idea of a COVID medicinal toolbox made up of different antiviral treatment modalities, and present some of the latest therapeutic strategies that are being explored in this respect to try to combat the COVID-19 virus and other COVID viruses that are predicted to follow. Lastly, we review current literature on the use of siRNA therapeutics as a way to remain adaptable and in tune with the ever-evolving mutation rate of the COVID-19 virus.

Photoacoustic Imaging Probes for Theranostic Applications.

Photoacoustic imaging (PAI), an emerging biomedical imaging technology, capitalizes on a wide range of endogenous chromophores and exogenous contrast agents to offer detailed information related to the functional and molecular content of diseased biological tissues. Compared with traditional imaging technologies, PAI offers outstanding advantages, such as a higher spatial resolution, deeper penetrability in biological tissues, and improved imaging contrast. Based on nanomaterials and small molecular organic dyes, a huge number of contrast agents have recently been developed as PAI probes for disease diagnosis and treatment. Herein, we report the recent advances in the development of nanomaterials and organic dye-based PAI probes. The current challenges in the field and future research directions for the designing and fabrication of PAI probes are proposed.