Controllable Generation of Nitric Oxide by Near‐Infrared‐Sensitized Upconversion Nanoparticles for Tumor Therapy

NaYbF₄:Tm@NaYF₄:Yb/Er upconversion nanoparticles are synthesized and then integrated with light‐sensitive nitric oxide (NO) donors (Roussin's black salt) to construct a novel near‐infrared (NIR)‐triggered on‐demand NO delivery platform. This nanocompound can absorb 980 nm NIR photons, convert them into higher energy photons and then transfer the energy to the NO donors, resulting in an efficient release of NO. By manipulating the output power of the 980‐nm NIR light, NO‐concentration‐dependent biological effects for cancer therapy can be fine‐tuned, which is investigated and confirmed in vitro. High concentrations of NO can directly kill cancer cells and low concentrations of NO can act as a potent P‐glycoprotein (P‐gp) modulator to overcome multi‐drug resistance (MDR) if combined with chemotherapy.     

Dendritic Fe3O4@Poly(dopamine)@PAMAM Nanocomposite as Controllable NO‐Releasing Material: A Synergistic Photothermal and NO Antibacterial Study

Nowadays, antibiotic abuse increases the emergence of multidrug‐resistant bacterial strains, which is the major reason for the failure of conventional antibiotic therapies. Therefore, developing novel antibacterial materials or therapies is an urgent demand. In the present study, photothermal and NO‐releasing properties are integrated into a single nanocomposite to realize more efficient bactericidal effects. To this end, polydopamine (PDA) coated iron oxide nanocomposite (Fe₃O₄@PDA) is used as a photoconversion agent and the core, first three generation dendritic poly(amidoamine) (PAMAM‐G3) is grafted on the surface of Fe₃O₄@PDA, and subsequently NO is loaded with the formation of NONOate. The resultant Fe₃O₄@PDA@PAMAM@NONOate displays controllable NO release property under intermittent 808 nm laser irradiation and excellent bacteria‐separation efficiency. Moreover, excellent synergistic photothermal and NO antibacterial effects are observed against both Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus, where bacterial viability and biofilm are significantly reduced. An antibacterial mechanism study reveals that the materials first adsorb onto the bacterial membrane, then cause damage to the membrane by the increased local temperature and the released NO under laser irradiation conditions, finally leak the intracellular components like DNA and induce bacteria death. The work provides a novel way for designing of antibacterial materials with higher efficiency.     

Near‐Infrared Laser‐Triggered Nitric Oxide Nanogenerators for the Reversal of Multidrug Resistance in Cancer

The potential therapeutic implications of nitric oxide (NO) for diverse diseases have been under consideration for years; however, the development of precisely controllable NO generation system with potential for clinical application has remained elusive. Herein, intelligent near‐infrared (NIR) laser‐triggered NO nanogenerators for the treatment of multidrug‐resistant (MDR) cancer are fabricated by integrating photothermal agents and heat‐sensitive NO donors into a single nanoparticle. Such nanogenerators can absorb 808 nm NIR photons and convert them into ample heat to trigger NO release. The generated NO molecules are demonstrated to successfully achieve multidrug‐resistance reversal by inhibiting the expression of P‐glycol protein. Consequently, the intracellular accumulation of doxorubicin is effectively increased, resulting in high toxicity to MDR cancer cells in vitro. By virtue of surface modification with targeting ligands, these nanoparticles are able to selectively accumulate in tumor tissue. The therapeutic effects of the nanogenerators are validated in a humanized MDR cancer model. The in vivo experiment indicates that the nanoparticles possess excellent tumor suppression functionality with few side effects upon NIR laser exposure. Therefore, this novel photothermal conversion‐based NO‐releasing platform is expected to be a potential alternative to clinical MDR cancer treatment and may provide insights with regard to other NO‐relevant medical treatments.     

Silver‐Infused Porphyrinic Metal–Organic Framework: Surface‐Adaptive,On‐Demand Nanoplatform for Synergistic Bacteria Killing and Wound Disinfection

The fabrication of functional nanoplatforms for combating multidrug‐resistant bacteria is of vital importance. Among them, silver nanoparticles (Ag NPs) have shown an antibacterial effect; however, the remainder cores of Ag NPs after use might have a toxic effect on humans. Thus, Ag ions based materials have been fabricated to substitute Ag NPs for antibacterial applications. Nevertheless, the always‐on release state leads to the low biocompatibility, which limits their biomedical applications. In addition, the single effect also restricts their antibacterial ability. Herein, a powerful surface‐adaptive, on‐demand antimicrobial nanoplatform is fabricated by coating hyaluronic acid (HA) on Ag ions loaded photosensitive metal‐organic frameworks to exhibit a strong synergistic effect. The nanoplatform shows good biocompatibility with nontargeted cells, as negatively charged HA can prevent the release of Ag ions. While in the presence of targeted bacteria, the secreted hyaluronidase can degrade HA on the nanoplatform and produce positively charged nanoparticles, which display increased affinity to bacteria and show a strong synergistic antibacterial effect owing to the released Ag ions and generated reactive oxygen species under visible light irradiation. Importantly, due to the outstanding on‐demand antimicrobial performance, the nanoplatform also shows great effects on treating multidrug‐resistant bacteria infected wounds in mice models.     

Surface‐Modified Mesoporous SiO2 Containers for Corrosion Protection

The development of active corrosion protection systems for metallic substrates is an issue of prime importance for many industrial applications. The present work shows a new contribution to the design of a new protective system based on surface modified mesoporous silica containers. Incorporation of silica‐based containers into special sol–gel matrix allows for a self‐healing effect to be achieved during the corrosion process. The self‐healing ability occurs due to release of entrapped corrosion inhibitors in response to pH changes caused by the corrosion process. A silica–zirconia‐based hybrid film is used in this work as a coating matrix deposited on AA2024 aluminum alloy. Mesoporous silica nano‐particles are covered layer‐by‐layer with polyelectrolyte layers and loaded with inhibitor [2‐(benzothiazol‐2‐ylsulfanyl)‐succinic acid]. The hybrid film with nanocontainers reveals enhanced long‐term corrosion protection in comparison with the individual sol–gel films. The scanning vibrating electrode technique also shows an effective healing ability of containers to cure the corrosion defects. This effect is due to the release of the corrosion inhibitor triggered by the corrosion processes started in the cavities. The approach described herein can be used in many applications where active corrosion protection of materials is required.     

Improvement of Biological Organisms Using Functional Material Shells

Biomineralization brings inorganic materials into biological organisms and it plays an important role in natural evolution. Inspired by biomineralized eggs and diatoms with protective shell structures, scientists have artificially endowed organisms with functional materials. The resulting organism–material hybrids become more robust and even evolve new functions. This feature article reviews recent achievements of organism improvements by various material shells and related applications in cell protection, storage, thermal stability, biological stealth, photosynthesis and biocatalysis, etc. Different from the previous understanding of biomineralization, the regulation effects of materials on organism functions are highlighted in these biomineralization‐inspired biological improvements, which present an artificial evolution strategy by using material techniques. We suggest that rationally designed organism–materials with optimized functions can shed light on solving global problems such as energy crisis and environmental pollution, as well as on improving medical treatment and intricate material designing. More generally, the studies of material‐based organism improvement can combine biological and material sciences together for a closer integration.     

Mimicking Cellular Signaling Pathways within Synthetic Multicompartment Vesicles with Triggered Enzyme Activity and Induced Ion Channel Recruitment

Subcellular compartmentalization of cells, a defining characteristic of eukaryotes, is fundamental for the fine tuning of internal processes and the responding to external stimuli. Reproducing and controlling such compartmentalized hierarchical organization, responsiveness, and communication is important toward understanding biological systems and applying them to smart materials. Herein, a cellular signal transduction strategy (triggered release from subcompartments) is leveraged to develop responsive, purely artificial, polymeric multicompartment assemblies. Incorporation of responsive nanoparticles—loaded with enzymatic substrate or ion channels—as subcompartments inside micrometer‐sized polymeric vesicles (polymersomes) allowed to conduct bioinspired signaling cascades. Response of these subcompartments to an externally added stimulus is achieved and studied by using confocal laser scanning microscopy (CLSM) coupled with in situ fluorescence correlation spectroscopy (FCS). Signal triggered activity of an enzymatic reaction is demonstrated in multicompartments through recombination of compartmentalized substrate and enzyme. In parallel, a two‐step signaling cascade is achieved by triggering the recruitment of ion channels from inner subcompartments to the vesicles' membrane, inducing ion permeability, mimicking endosome‐mediated insertion of internally stored channels. This design shows remarkable versatility, robustness, and controllability, demonstrating that multicompartment polymer‐based assemblies offer an ideal scaffold for the development of complex cell‐inspired responsive systems for applications in biosensing, catalysis, and medicine.     

Slippery Liquid‐Infused Porous Surfaces that Prevent Microbial Surface Fouling and Kill Non‐Adherent Pathogens in Surrounding Media: A Controlled Release Approach

Many types of slippery liquid‐infused porous surfaces (‘SLIPS’) can resist adhesion and colonization by microorganisms. These ‘slippery’ materials thus offer approaches to prevent fouling on commercial and industrial surfaces. However, while SLIPS can prevent fouling on surfaces to which they are applied, they can currently do little to prevent the proliferation of non‐adherent organisms. Here, multi‐functional SLIPS are reported that address this issue and expand the potential utility of these materials. The approach is based on the release of antimicrobial agents from the porous matrices used to host the infused oil phases. It is demonstrated that SLIPS fabricated from nanoporous polymer multilayers can prevent colonization and biofilm formation by four common fungal and bacterial pathogens, and that the polymer and oil phases comprising these materials can be used to sustain the release of triclosan, a model antimicrobial agent, into surrounding media. This approach improves the inherent anti‐fouling properties of these materials and endows them with the ability to kill non‐adherent pathogens. This strategy has the potential to be general; the strategies and concepts reported here will enable the design of SLIPS with improved anti‐fouling properties and open the door to new applications of slippery liquid‐infused materials that host or release other active agents.     

Multifunctional Hybrid Polymer‐Based Porous Materials

Polymer‐based porous hybrid materials (PHMs) carrying inorganic nanoparticles on the surface of pores have important applications in chemical and biological sensing, in chromatography, and in heterogeneous catalysis. This Feature Article provides an overview of the recent developments in the synthesis and fabrication of multifunctional PHMs using polymerization‐induced phase separation. Exemplary applications of a PHM coated with gold nanorods were demonstrated for the simultaneous detection of different analytes using surface enhanced Raman scattering (SERS) spectroscopy and fluorescence microscopy.     

Electrospinning of Manmade and Biopolymer Nanofibers—Progress in Techniques,Materials, and Applications

Electrospinning of nanofibers has developed quickly from a laboratory curiosity to a highly versatile method for the preparation of a wide variety of nanofibers, which are of interest from a fundamental as well as a technical point of view. A wide variety of materials has been processed into individual nanofibers or nanofiber mats with very different morphologies. The diverse properties of these nanofibers, based on different physical, chemical, or biological behavior, mean they are of interest for different applications ranging from filtration, antibacterial coatings, drug release formulations, tissue engineering, living membranes, sensors, and so on. A particular advantage of electrospinning is that numerous non‐fiber forming materials can be immobilized by electrospinning in nanofiber nonwovens, even very sensitive biological objects such as virus, bacteria, and cells. The progress made during the last few years in the field of electrospinning is fascinating and is highlighted in this Feature Article, with particular emphasis on results obtained in the authors' research units. Specific areas of importance for the future of electrospinning, and which may open up novel applications, are also highlighted.     

Water‐Powered Cell‐Mimicking Janus Micromotor

Cell derivatives have received increasing attention due to their unique ability to mimic many of the natural properties displayed by their source cells. Integration of cell‐derived natural materials with synthetic subjects can be applied toward the development of novel biomedical nano/microscale devices for a wide range of applications, including drug delivery and biodetoxification. Herein, a cell membrane functionalized magnesium‐based Janus micromotor, powered by water, that mimics natural motile cells is reported. The new cell‐mimicking Janus micromotor is constructed by integrating red blood cell (RBC) membranes, gold nanoparticles (AuNPs), and alginate (ALG) onto the exposed surface areas of magnesium microparticles that are partially embedded in Parafilm. The resulting RBC membrane‐coated magnesium (RBC‐Mg) Janus micromotors display an efficient and guided propulsion in water without any external fuel, as well as in biological (albumin‐rich) media with no apparent biofouling, mimicking the movement of natural motile cells. The effective RBC membrane coating bestows the RBC‐Mg Janus micromotors with unique capability for absorbing and neutralizing both biological protein toxins and nerve agent simulants. Such detoxification ability is facilitated greatly by the water‐driven motion of the motors. The RBC‐Mg Janus micromotors represent an exciting progress toward cell‐mimicking microscale motors that hold great promise for diverse biomedical and biodefense applications.     

Interfacial Assembly of Mesoporous Silica‐Based Optical Heterostructures for Sensing Applications

Functionalized mesoporous silica materials (MSMs) are extensively investigated in sensing science due to their diverse structural and optical properties including tunable pore size, modifiable surface properties, and excellent accessibility to active sites. In the last few years, great efforts have been devoted to developing modification methods for MSMs for sensing applications with augmented sensitivity, super selectivity, as well as targeting capability, and multimodal capabilities. The functional group, structure, morphology, and component levels in the assembly of heterostructures of MSMs are a key for high sensing performance. As the development of mesoporous silica‐based sensing materials progresses, diverse functional units and materials are rationally implemented into the mesoporous structures. These heterostructures can maintain the excellent structural features of mesoporous silica and the optical properties of the functional units simultaneously, which shows the advantages of photostability, design flexibility, and multifunctionality. Here, an up‐to‐date overview of the fabrication strategies, the properties, and the sensing mechanisms of optical heterostructures based on MSMs is provided. A number of crucial sensing domains, including ionic, molecules, temperature, and biological species are highlighted. Finally, the prospects and potential sensing applications of mesoporous silica‐based optical heterostructures are discussed.     

Bioinspired Material Approaches to Sensing

Bioinspired design is an engineering approach that involves working to understand the design principles and strategies employed by biology in order to benefit the development of engineered systems. From a materials perspective, biology offers an almost limitless source of novel approaches capable of arousing innovation in every aspect of materials, including fabrication, design, and functionality. Here, recent and ongoing work on the study of bioinspired materials for sensing applications is presented. Work presented includes the study of fish flow receptor structures and the subsequent development of similar structures to improve flow sensor performance. The study of spider air‐flow receptors and the development of a spider‐inspired flexible hair is also discussed. Lastly, the development of flexible membrane based infrared sensors, highly influenced by the fire beetle, is presented, where a pneumatic mechanism and a thermal‐expansion stress‐mediated buckling‐based mechanism are investigated. Other areas that are discussed include novel biological signal filtering mechanisms and reciprocal benefits offered through applying the biology lessons to engineered systems.     

Polyelectrolyte Blend Multilayers: A Versatile Route to Engineering Interfaces and Films

The ability to reliably engineer surfaces with nanoscale precision is a rapidly developing field of research with applications ranging from biosensing and biomedical materials to antifouling and corrosion protection. The layer‐by‐layer (LbL) approach is a widely utilized method for engineering surfaces, in part because of the large array of polymeric materials that can be integrated and the diverse range of functionality that these materials afford. Herein, we discuss the LbL deposition of multicomponent ‘blend' solutions to form polyelectrolyte blend multilayer films and coatings. This approach is a versatile platform for enhancing film stability, incorporating a wide range of functional materials, controlling film morphology and material properties, and increasing biological response, thereby expanding the range of potential applications.     

Stimuli‐Responsive Materials for Controlled Release of Theranostic Agents

Stimuli‐responsive materials are so named because they can alter their physicochemical properties and/or structural conformations in response to specific stimuli. The stimuli can be internal, such as physiological or pathological variations in the target cells/tissues, or external, such as optical and ultrasound radiations. In recent years, these materials have gained increasing interest in biomedical applications due to their potential for spatially and temporally controlled release of theranostic agents in response to the specific stimuli. This article highlights several recent advances in the development of such materials, with a focus on their molecular designs and formulations. The future of stimuli‐responsive materials will also be explored, including combination with molecular imaging probes and targeting moieties, which could enable simultaneous diagnosis and treatment of a specific disease, as well as multi‐functionality and responsiveness to multiple stimuli, all important in overcoming intrinsic biological barriers and increasing clinical viability.     

Two‐Dimensional Transition Metal Dichalcogenides in Biosystems

The intriguing properties of two‐dimensional transition metal dichalcogenides (2D TMDCs) have led to a significant body of fundamental research and rapid uptake of these materials in many applications. Specifically, 2D TMDCs have shown great potential in biological systems due to their tunable electronic characteristics, unique optical properties, stability in aqueous environments, large surface area that can be manipulated and functionalized as well as an intercalatable layered structure, and low levels of toxicity. Here, the characteristics and use of 2D TMDCs for biological applications are reviewed and future possibilities for these materials in biological systems are outlined.     

Rapid Generation of Biologically Relevant Hydrogels Containing Long‐Range Chemical Gradients

Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue‐mimetic constructs. Here a simple and versatile method to rapidly generate materials containing centimeter‐long gradients of chemical properties in a microfluidic channel is described. The formation of a chemical gradient is initiated by a passive‐pump‐induced forward flow and further developed during an evaporation‐induced backward flow. The gradient is spatially controlled by the backward flow time and the hydrogel material containing the gradient is synthesized via photopolymerization. Gradients of a cell‐adhesion ligand, Arg‐Gly‐Asp‐Ser (RGDS), are incorporated in poly(ethylene glycol)‐diacrylate (PEG‐DA) hydrogels to test the response of endothelial cells. The cells attach and spread along the hydrogel material in a manner consistent with the RGDS‐gradient profile. A hydrogel containing a PEG‐DA concentration gradient and constant RGDS concentration is also shown. The morphology of cells cultured on such hydrogel changes from round in the lower PEG‐DA concentration regions to well‐spread in the higher PEG‐DA concentration regions. This approach is expected to be a valuable tool to investigate the cell–material interactions in a simple and high‐throughput manner and to design graded biomimetic materials for tissue engineering applications.     

Versatile Microfluidic Platforms Enabled by Novel Magnetorheological Elastomer Microactuators

Microfluidic systems enable rapid diagnosis of diseases, biological analysis, drug screening, and high‐precision materials synthesis. In spite of these remarkable abilities, conventional microfluidic systems are microfabricated monolithically on a single platform and their operations rely on bulky expensive external equipment. This restricts their applications outside of research laboratories and prevents development and assembly of truly versatile and complex systems. Here, novel magnetorheological elastomer (MRE) microactuators are presented including pumps and mixers using an innovative actuation mechanism without the need of delicate elements such as thin membranes. Modularized elements are realized using such actuators, which can be easily integrated and actuated using a single self‐contained driving unit to create a modular, miniaturized, and robust platform. The performance of the microactuators is investigated via a series of experiments and a proof‐of‐concept modular system is developed to demonstrate the viability of the platform for self‐contained applications. The presented MRE microactuators are small size, simple, and efficient, offering a great potential to significantly advance the current research on complex microfluidic systems.     

Versatile Antibacterial Materials: An Emerging Arsenal for Combatting Bacterial Pathogens

Antibacterial materials that prevent bacterial infections and mitigate bacterial virulence have attracted great scientific interests. In recent decades, the bactericidal polymers have been presented as promising candidates to combat bacterial pathogens, mainly based on the construction of bactericidal cationic polymers, functionalization with biocidal agents, and formation of bacterial‐repelling layers. However, these established strategies have inherent disadvantages because they often overlook important features such as their biocompatibility and biosafety, especially for biomedical applications. In recent years, many efforts have been made focusing on the development of multifunctional antibacterial materials to meet the elaborate requirements for medical devices and public hygiene products. Herein the recent advances in developing multifunctional materials for their antibacterial activities together with other functions including “kill‐and‐release” capability, hemocompatibility, cell proliferation promoting properties, and coagulation promoting ability for wound dressing are highlighted. In addition, the outlooks on the remaining challenges that should be addressed in the field of multifunctional antibacterial materials are also described.     

Biodegradable Frequency‐Selective Magnesium Radio‐Frequency Microresonators for Transient Biomedical Implants

Bioresorbable implantable medical devices show a great potential for applications requiring medical care over well‐defined periods of time. Once their function is fulfilled, such implants naturally degrade and resorb in the body, which eliminates adverse long‐term effects or the need for a secondary surgery to extract the implanted device. Since biodegradable materials are water‐soluble, the fabrication of such transient electronic circuits and devices requires special care and needs to rely solely on dry processing steps without exposure to aqueous solutions. A further challenge is the in vivo powering of medical implants that are only constituted of biodegradable materials. This paper describes the design, fabrication, and testing of radio‐frequency biodegradable magnesium microresonators. To this end, an innovative microfabrication process with minimal exposure to aqueous media is developed to fabricate magnesium‐based, water‐soluble electronic components. It consists of a novel sequence of only three steps: one physical vapor deposition, one photolithography, and one ion beam etching step. The frequency‐selective wireless heating of different resonators is demonstrated. This represents a significant step toward their use as power receivers and microheaters in biodegradable implantable medical devices, for applications such as triggered drug release.