Enhanced Anticancer Efficacy by ATP‐Mediated Liposomal Drug Delivery

A liposome‐based co‐delivery system composed of a fusogenic liposome encapsulating ATP‐responsive elements with chemotherapeutics and a liposome containing ATP was developed for ATP‐mediated drug release triggered by liposomal fusion. The fusogenic liposome had a protein–DNA complex core containing an ATP‐responsive DNA scaffold with doxorubicin (DOX) and could release DOX through a conformational change from the duplex to the aptamer/ATP complex in the presence of ATP. A cell‐penetrating peptide‐modified fusogenic liposomal membrane was coated on the core, which had an acid‐triggered fusogenic potential with the ATP‐loaded liposomes or endosomes/lysosomes. Directly delivering extrinsic liposomal ATP promoted the drug release from the fusogenic liposome in the acidic intracellular compartments upon a pH‐sensitive membrane fusion and anticancer efficacy was enhanced both in vitro and in vivo.     

Redox‐Sensitive Stomatocyte Nanomotors: Destruction and Drug Release in the Presence of Glutathione

The development of artificial nanomotor systems that are stimuli‐responsive is still posing many challenges. Herein, we demonstrate the self‐assembly of a redox‐responsive stomatocyte nanomotor system, which can be used for triggered drug release under biological reducing conditions. The redox sensitivity was introduced by incorporating a disulfide bridge between the hydrophilic poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated with the endogenous reducing agent glutathione at a concentration comparable to that within cells, the external PEG shells of these stimuli‐responsive nanomotors are cleaved. The specific bowl‐shaped stomatocytes aggregate after the treatment with glutathione, leading to the loss of motion and triggered drug release. These novel redox‐responsive nanomotors can not only be used for remote transport but also for drug delivery, which is promising for future biomedical applications.     

Multiple Light Control Mechanisms in ATP‐Fueled Non‐equilibrium DNA Systems

Fuel‐driven self‐assemblies are gaining ground for creating autonomous systems and materials, whose temporal behavior is preprogrammed by a reaction network. However, up to now there has been a lack of simple external control mechanisms of the transient behavior, at best using remote and benign light control. Even more challenging is to use different wavelengths to modulate the reactivity of different components of the system, for example, as fuel or building blocks. Success would enable such systems to navigate along different trajectories in a wavelength‐dependent fashion. Herein, we introduce the first examples of light control in ATP‐fueled, dynamic covalent DNA polymerization systems organized in an enzymatic reaction network of concurrent ATP‐powered ligation and restriction. We demonstrate concepts for light activation and modulation by introducing caged ATP derivatives and caged DNA building blocks, making it possible to realize light‐activated fueling, self‐sorting in structure and behavior, and transition across different wavelength‐dependent dynamic steady states.     

Fuel‐Selective Transient Activation of Nanosystems for Signal Generation

The transient activation of function using chemical fuels is common in nature, but much less in synthetic systems. Progress towards the development of systems with a complexity similar to that of natural ones requires chemical fuel selectivity. Here, we show that a self‐assembled nanosystem, composed of monolayer‐protected gold nanoparticles and a fluorogenic peptide, is activated for transient signal generation only in case the chemical fuel matches the recognition site present at the nanoparticle surface. A modification of the recognition site in the nanosystem completely changes the chemical fuel selectivity. When two nanosystems are simultaneously present, the selectivity expressed by the system depends on the concentration of nucleotide added.     

Catalysis‐Driven Self‐Thermophoresis of Janus Plasmonic Nanomotors

It is highly demanding to design active nanomotors that can move in response to specific signals with controllable rate and direction. A catalysis‐driven nanomotor was constructed by designing catalytically and plasmonically active Janus gold nanoparticles (Au NPs), which generate an asymmetric temperature gradient of local solvent surrounding NPs in catalytic reactions. The self‐thermophoresis behavior of the Janus nanomotor is monitored from its inherent plasmonic response. The diffusion coefficient of the self‐thermophoresis motion is linearly dependent on chemical reaction rate, as described by a stochastic model.     

ATP‐Releasing Nucleotides: Linking DNA Synthesis to Luciferase Signaling

A new strategy is reported for the production of luminescence signals from DNA synthesis through the use of chimeric nucleoside tetraphosphate dimers in which ATP, rather than pyrophosphate, is the leaving group. ATP‐releasing nucleotides (ARNs) were synthesized as derivatives of the four canonical nucleotides. All four derivatives are good substrates for DNA polymerase, with K_m values averaging 13‐fold higher than those of natural dNTPs, and k_cat values within 1.5‐fold of those of native nucleotides. Importantly, ARNs were found to yield very little background signal with luciferase. DNA synthesis experiments show that the ATP byproduct can be harnessed to elicit a chemiluminescence signal in the presence of luciferase. When using a polymerase together with the chimeric nucleotides, target DNAs/RNAs trigger the release of stoichiometrically large quantities of ATP, thereby allowing sensitive isothermal luminescence detection of nucleic acids as diverse as phage DNAs and short miRNAs.     

Multi‐Light‐Responsive Quantum Dot Sensitized Hybrid Micromotors with Dual‐Mode Propulsion

CdS quantum dots/C₆₀ tubular micromotors with chemical/multi‐light‐controlled propulsion and “on‐the‐fly” acceleration capabilities are described. In situ growth of CdS quantum dots on the outer fullerene layer imparts this layer with light‐responsive properties in connection to inner Pt, Pd or MnO₂ layers. This is the first time that visible light is used to drive bubble‐propelled tubular micromotors. The micromotors exhibit a broad absorption range from 320 to 670 nm and can be wirelessly controlled by modulating light intensity and peroxide concentration. The built‐in accelerating optical system allows for the control of the velocity over the entire UV/Vis light spectra by modulating the catalyst surface chemistry. The light‐responsive properties have been also exploited to accelerate the chemical dealloying and propulsion of micromotors containing a Cu/Pd layer. Such dual operated hybrid micromotors hold considerable promise for designing smart micromachines for on‐demand operations, motion‐based sensing, and enhanced cargo transportation.     

Light‐Activated Active Colloid Ribbons

We report a dynamic self‐organization of self‐propelled peanut‐shaped hematite motors from non‐equilibrium driving forces where the propulsion can be triggered by blue light. They result in one‐dimensional, active colloid ribbons with a positive phototactic characteristic. The motion of colloid motors is ascribed to the diffusion‐osmotic flow in a chemical gradient by the photocatalytic decomposition of hydrogen peroxide fuel. We show that self‐propelled peanut‐shaped colloids readily form one‐dimensional, slithering ribbon structures under the out‐of‐equilibrium collisions. This self‐organization intrinsically results from the competition among the osmotically driven motion, the phoretic attraction and the inherent magnetic moments. The giant size number fluctuation in colloid ribbons is observed above a critical point 4.1 % of the surface density of colloid motors. Such phototactic colloid ribbons may provide a model system to understand the emergence of function in biological systems and have potential to construct bioinspired active materials based on different active building blocks.     

Accelerated Self‐Replication under Non‐Equilibrium,Periodic Energy Delivery

Self‐replication is a remarkable phenomenon in nature that has fascinated scientists for decades. In a self‐replicating system, the original units are attracted to a template, which induce their binding. In equilibrium, the energy required to disassemble the newly assembled copy from the mother template is supplied by thermal energy. The possibility of optimizing self‐replication was explored by controlling the frequency at which energy is supplied to the system. A model system inspired by a class of light‐switchable colloids was considered where light is used to control the interactions. Conditions under which self‐replication can be significantly more effective under non‐equilibrium, cyclic energy delivery than under equilibrium constant energy conditions were identified. Optimal self‐replication does not require constant energy expenditure. Instead, the proper timing at which energy is delivered to the system is an essential controllable parameter to induce high replication rates.     

Tuneable Transient Thermogels Mediated by a pH‐ and Redox‐Regulated Supramolecular Polymerization

A multistimuli‐responsive transient supramolecular polymerization of β‐sheet‐encoded dendritic peptide monomers in water is presented. The amphiphiles, which contain glutamic acid and methionine, undergo a glucose oxidase catalyzed, glucose‐fueled transient hydrogelation in response to an interplay of pH and oxidation stimuli, promoted by the production of reactive oxygen species (ROS). Adjusting the enzyme and glucose concentration allows tuning of the assembly and the disassembly rates of the supramolecular polymers, which dictate the stiffness and transient stability of the hydrogels. The incorporation of triethylene glycol chains introduces thermoresponsive properties to the materials. We further show that repair enzymes are able to reverse the oxidative damage in the methionine‐based thioether side chains. Since ROS play an important role in signal transduction cascades, our strategy offers great potential for applications of these dynamic biomaterials in redox microenvironments.     

TargetATPsite: A template‐free method for ATP‐binding sites prediction with residue evolution image sparse representation and classifier ensemble

Understanding the interactions between proteins and ligands is critical for protein function annotations and drug discovery. We report a new sequence‐based template‐free predictor (TargetATPsite) to identify the Adenosine‐5′‐triphosphate (ATP) binding sites with machine‐learning approaches. Two steps are implemented in TargetATPsite: binding residues and pockets predictions, respectively. To predict the binding residues, a novel image sparse representation technique is proposed to encode residue evolution information treated as the input features. An ensemble classifier constructed based on support vector machines (SVM) from multiple random under‐samplings is used as the prediction model, which is effective for dealing with imbalance phenomenon between the positive and negative training samples. Compared with the existing ATP‐specific sequence‐based predictors, TargetATPsite is featured by the second step of possessing the capability of further identifying the binding pockets from the predicted binding residues through a spatial clustering algorithm. Experimental results on three benchmark datasets demonstrate the efficacy of TargetATPsite. © 2013 Wiley Periodicals, Inc.     

Therapeutic Vesicular Nanoreactors with Tumor‐Specific Activation and Self‐Destruction for Synergistic Tumor Ablation

Polymeric nanoreactors (NRs) have distinct advantages to improve chemical reaction efficiency, but the in vivo applications are limited by lack of tissue‐specificity. Herein, novel glucose oxidase (GOD)‐loaded therapeutic vesicular NRs (thera NR) are constructed based on a diblock copolymer containing poly(ethylene glycol) (PEG) and copolymerized phenylboronic ester or piperidine‐functionalized methacrylate (P(PBEM‐co ‐PEM)). Upon systemic injection, thera NR are inactive in normal tissues. At a tumor site, thera NR are specifically activated by the tumor acidity via improved permeability of the membranes. Hydrogen peroxide (H₂O₂) production by the catalysis of GOD in thera NR increases tumor oxidative stress significantly. Meanwhile, high levels of H₂O₂ induce self‐destruction of thera NR releasing quinone methide (QM) to deplete glutathione and suppress the antioxidant ability of cancer cells. Finally, thera NR efficiently kill cancer cells and ablate tumors via the synergistic effect.     

Nanotechnology‐Enabled Energy Harvesting for Self‐Powered Micro‐/Nanosystems

Health, infrastructure, and environmental monitoring as well as networking and defense technologies are only some of the potential areas of application of micro‐/nanosystems (MNSs). It is highly desirable that these MNSs operate without an external electricity source and instead draw the energy they require from the environment in which they are used. This Review covers various approaches for energy harvesting to meet the future demand for self‐powered MNSs.