stimuli generate driving forces from the interaction between the micro/nanorobots and aspects of the treatment microenvironment, such as pH, enzymes, and redox potential. [4][5][6][7][8][9] However, the controllability of endogenous power-driven cell robots is limited, considering tumor heterogeneity. In addition, the cell robots may lose driving force when local lesions are cured. In contrast, driving forces generated from externally-applied fields are controllable, and can be output continuously. Micro/ nanorobots for biomedical applications, driven by optical, [9][10][11][12][13] acoustic, [14][15][16][17][18] or magnetic fields, [19][20][21][22][23] have been reported. In particular, micro/nanorobots controlled by magnetic fields have been studied extensively, because magnetic fields can penetrate tissues without attenuation of energy. [23][24][25][26] In general, magneticallycontrolled micro/nanorobot systems can be divided into two components: the magnetic manipulation platform (MMP), and the magnetized micro/nanorobot (MMR). The MMP relies primarily on the characteristics of superimposed magnetic fields, generated by different coils, that can be oriented in any desired direction. [27,28] To be biocompatible, cell membranes, [29] cell derived vesicles, [30] or natural cells [31,32] can be used to camouflage MMRs. [33] Magnetized cell-based robots (MCRs) are particularly effective in targeted treatment of tumors, owing to their homology with the patient, which not only gives the cell carrier excellent biocompatibility, but also takes advantage of the cells' specialized functions. [34,35] MCR fabrication is typically manifested as adhesion of magnetic materials to the cell membrane, or entry of magnetic materials to the cell by means, such as electrostatic adsorption or endocytosis. Examples of the latter strategy include the loading of red blood cells, [36][37][38] macrophages, [32,39] and stem cells [40,41] with iron oxide nanoparticles (NPs) containing drugs, for effective targeting of lesion locations under magnetic drive. However, with this strategy, drug loading is limited, to avoid influencing the activity of cells. An alternative strategy is to wrap the drugs in a membrane, and release them when the cell robots reach the lesion location. For example, liposome or polymer NPs can be loaded into live macrophages thanks to their natural phagocytic function, and the load-drugs can subsequently be released under endogenous or exogenous Injecting micro/nanorobots into the body to kill tumors is one of the ultimate ambitions for medical nanotechnology. However, injecting current micro/ nanorobots based on 3D-printed biocompatible materials directly into blood vessels for targeted therapy is often difficult, and mistakes in targeting can cause serious side effects, such as blood clots, oxidative stress, or inflammation. The natural affinity of macrophages to tumors, and their natural phagocytosis and ability to invade tumors, make them outstanding drug delivery vehicles for targeted tumor therapy. Hence, a mag...
Polymer-based fluorescent nanomaterials have proven to universally image various tumors based on their extremely sharp responsiveness to pH change. Such a property has never been realized in supramolecular systems. We herein design a small molecule (DPP-thiophene-4) that is composed of a diketopyrrolopyrrole (DPP) core and two alkyl chains terminated with quaternary ammonium. DPP-thiophene-4 can self-assemble into a nonfluorescent nanoassembly when the pH is >7.0 but reversibly disassembles back to fluorescent monomers when the pH is <6.8. Meanwhile, its fluorescence emission increases by 10-fold within a 0.2 pH unit change. Such a fluorogenic nanoassembly can precisely differentiate a number of malignant tumors among normal tissues in vivo due to the slight acidity within tumor microenvironments. Further the nanoassembly shows satisfactory biocompatibility and an effective clearance from the body. Overall, this supramolecular fluorogenic nanoassembly exhibits an immense potential for realizing broad range tumor diagnosis.
Abstract. The Succinct Solver Suite offers two analysis engines for solving data and control flow problems expressed in clausal form in a large fragment of first order logic. The solvers have proved to be useful for a variety of applications including security properties of Java Card bytecode, access control features of Mobile and Discretionary Ambients, and validation of protocol narrations formalised in a suitable process algebra. Both solvers operate over finite domains although they can cope with regular sets of trees by direct encoding of the tree grammars; they differ in fine details about the demands on the universe and the extent to which universal quantification is allowed. A number of transformation strategies, mainly automatic, have been studied aiming on the one hand to increase the efficiency of the solving process, and on the other hand to increase the ease with which users can develop analyses. The results from benchmarking against state-of-the-art solvers are encouraging.
with efficient locomotion in fluids. Particularly, in fields that require biosafety, these robots need to be biofriendly, biocompatible, and multifunctional. In recent years, cell membrane-coated microrobots were designed, which provided new possibilities for researchers to easily harness native biological functions. [10,11] Additionally, biological template-based microrobots, such as bacterium-based robots, [12,13] sperm-based robots, [14] and cell-based motors, [15,16] have extraordinary properties while maintaining their original functionality. By providing these biological robots with new characteristics, they can be propelled by an external field to achieve various functions. For example, researchers have created cell-based delivery systems with the property of low toxicity and immunogenicity including the red blood cells, [17] platelets, [18] stem cells, [19] immune cells, [20] and tumor cells [21] that could be controlled to achieve precise site-specific delivery with better treatment efficacy. [22,23] Recently, magnetically propelled microrobots have gained particular attention in the bioengineering field, since magnetic fields are capable of penetrating most materials with minimal interaction and are nearly harmless. [24][25][26][27][28][29] Inspiringly, these magnetically actuated robots demonstrate flexible controllability to navigate mazes and could be used to manipulate cells precisely. [30,31] Exposed to a magnetic field, different magneticdriven microrobots can be controlled simultaneously and wirelessly with high precision. Therefore, microrobotic swarm behavior emerges when a large number of magnetic robots are activated by an external field. Although a single microrobot can achieve complex tasks, the power of an individual is always limited. In nature, swarm behavior appears everywhere. Specifically, bees collaborate to work efficiently, ant colonies work together to carry larger objects, and a school of fish swim together to resist predators. In the microworld, a magnetically driven robot swarm is promising because the swarm has a flexible morphology, [32] can travel through narrow channels, [33,34] and can even be observed in real organisms. [35] However, the implementation of biocompatible and biofriendly robot swarms is still a challenge.Immune cells are widely known as excellent carriers for targeted drug delivery, [36][37][38][39][40] owing to their capability to be decorated with functional nanoparticles. For robotics and cell manipulation, using a single cell robot to manipulate other Border-nearing microrobots with self-propelling and navigating capabilities have promising applications in micromanipulation and bioengineering, because they can stimulate the surrounding fluid flow for object transportation. However, ensuring the biosafety of microrobots is a concurrent challenge in bioengineering applications. Here, macrophage template-based microrobots (cell robots) that can be controlled individually or in chain-like swarms are proposed, which can transport various objects. The cell rob...
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