Insights into the Biological Activity and Bio-Interaction Properties of Nanoscale Imine-Based 2D and 3D Covalent Organic Frameworks.

Covalent Organic Frameworks (COFs) emerged as versatile materials with promising potential in  biomedicine. Their customizable functionalities and tunable pore structures make them valuable for various biomedical applications such as biosensing, bioimaging, antimicrobial activity, and targeted drug delivery. Despite efforts made to create nanoscale COFs (nCOFs) to enhance their interaction with biological systems, a comprehensive understanding of their inherent biological activities remains a significant challenge. In this study, a thorough investigation is conducted into the biocompatibility and anti-neoplastic properties of two distinct imine-based nCOFs. The approach involved an in-depth analysis of these nCOFs through in vitro experiments with various cell types and in vivo assessments using murine models. These findings revealed significant cytotoxic effects on tumor cells. Moreover, the activation of multiple cellular death pathways, including apoptosis, necroptosis, and ferroptosis is determined, supported by evidence at the molecular level. In vivo evaluations exhibited marked inhibition of tumor growth, associated with the elevated spontaneous accumulation of nCOFs in tumor tissues and the modulation of cell death-related protein expression. The research contributes to developing a roadmap for the characterization of the intricate interactions between nCOFs and biological systems and opens new avenues for exploiting their therapeutic potential in advanced biomedical applications.

Shape-Morphing in Oxide Ceramic Kirigami Nanomembranes.

Interfacial strain engineering in ferroic nanomembranes can broaden the scope of ferroic nanomembrane assembly as well as facilitate the engineering of multiferroic-based devices with enhanced functionalities. Geometrical engineering in these material systems enables the realization of 3-D architectures with unconventional physical properties. Here, 3-D multiferroic architectures are introduced by incorporating barium titanate (BaTiO3, BTO) and cobalt ferrite (CoFe2O4, CFO) bilayer nanomembranes. Using photolithography and substrate etching techniques, complex 3-D microarchitectures including helices, arcs, and kirigami-inspired frames are developed. These 3-D architectures exhibit remarkable mechanical deformation capabilities, which can be attributed to the superelastic behavior of the membranes and geometric configurations. It is also demonstrated that dynamic shape reconfiguration of these nanomembrane architectures under electron beam exposure showcases their potential as electrically actuated microgrippers and for other micromechanical applications. This research highlights the versatility and promise of multi-dimensional ferroic nanomembrane architectures in the fields of micro actuation, soft robotics, and adaptive structures, paving the way for incorporating these architectures into stimulus-responsive materials and devices.

Magnetically Guided Microcatheter for Targeted Injection of Magnetic Particle Swarms.

The initial delivery of small-scale magnetic devices such as microrobots is a key, but often overlooked, aspect for their use in clinical applications. The deployment of these devices within the dynamic environment of the human body presents significant challenges due to their dispersion caused by circulatory flows. Here, a method is introduced to effectively deliver a swarm of magnetic nanoparticles in fluidic flows. This approach integrates a magnetically navigated robotic microcatheter equipped with a reservoir for storing the magnetic nanoparticles. The microfluidic flow within the reservoir facilitates the injection of magnetic nanoparticles into the fluid stream, and a magnetic field gradient guides the swarm through the oscillatory flow to a target site. The microcatheter and reservoir are engineered to enable magnetic steering and injection of the magnetic nanoparticles. To demonstrate this approach, experiments are conducted utilizing a spinal cord phantom simulating intrathecal catheter delivery for applications in the central nervous system. These results demonstrate that the proposed microcatheter successfully concentrates nanoparticles near the desired location through the precise manipulation of magnetic field gradients, offering a promising solution for the controlled deployment of untethered magnetic micro-/nanodevices within the complex physiological circulatory systems of the human body.

A Naturally Inspired Extrusion-Based Microfluidic Approach for Manufacturing Tailorable Magnetic Soft Continuum Microrobotic Devices.

Soft materials play a crucial role in small-scale robotic applications by closely mimicking the complex motion and morphing behavior of organisms. However, conventional fabrication methods face challenges in creating highly integrated small-scale soft devices. In this study, microfluidics is leveraged to precisely control reaction-diffusion (RD) processes to generate multifunctional and compartmentalized calcium-cross-linkable alginate-based microfibers. Under RD conditions, sophisticated alginate-based fibers are produced for magnetic soft continuum robotics applications with customizable features, such as geometry (compact or hollow), degree of cross-linking, and the precise localization of magnetic nanoparticles (inside the core, surrounding the fiber, or on one side). This fine control allows for tuning the stiffness and magnetic responsiveness of the microfibers. Additionally, chemically cleavable regions within the fibers enable disassembly into smaller robotic units or roll-up structures under a rotating magnetic field. These findings demonstrate the versatility of microfluidics in processing highly integrated small-scale devices.

Multilevel design and construction in nanomembrane rolling for three-dimensional angle-sensitive photodetection.

Releasing pre-strained two-dimensional nanomembranes to assemble on-chip three-dimensional devices is crucial for upcoming advanced electronic and optoelectronic applications. However, the release process is affected by many unclear factors, hindering the transition from laboratory to industrial applications. Here, we propose a quasistatic multilevel finite element modeling to assemble three-dimensional structures from two-dimensional nanomembranes and offer verification results by various bilayer nanomembranes. Take Si/Cr nanomembrane as an example, we confirm that the three-dimensional structural formation is governed by both the minimum energy state and the geometric constraints imposed by the edges of the sacrificial layer. Large-scale, high-yield fabrication of three-dimensional structures is achieved, and two distinct three-dimensional structures are assembled from the same precursor. Six types of three-dimensional Si/Cr photodetectors are then prepared to resolve the incident angle of light with a deep neural network model, opening up possibilities for the design and manufacturing methods of More-than-Moore-era devices.

On-Command Disassembly of Microrobotic Superstructures for Transport and Delivery of Magnetic Micromachines.

Magnetic microrobots have been developed for navigating microscale environments by means of remote magnetic fields. However, limited propulsion speeds at small scales remain an issue in the maneuverability of these devices as magnetic force and torque are proportional to their magnetic volume. Here, a microrobotic superstructure is proposed, which, as analogous to a supramolecular system, consists of two or more microrobotic units that are interconnected and organized through a physical (transient) component (a polymeric frame or a thread). The superstructures consist of microfabricated magnetic helical micromachines interlocked by a magnetic gelatin nanocomposite containing iron oxide nanoparticles (IONPs). While the microhelices enable the motion of the superstructure, the IONPs serve as heating transducers for dissolving the gelatin chassis via magnetic hyperthermia. In a practical demonstration, the superstructure's motion with a gradient magnetic field in a large channel, the disassembly of the superstructure and release of the helical micromachines by a high-frequency alternating magnetic field, and the corkscrew locomotion of the released helices through a small channel via a rotating magnetic field, is showcased. This adaptable microrobotic superstructure reacts to different magnetic inputs, which can be used to perform complex delivery procedures within intricate regions of the human body.

"On-The-Fly" Synthesis of Self-Supported LDH Hollow Structures Through Controlled Microfluidic Reaction-Diffusion Conditions.

Layered double hydroxides (LDHs) are a class of functional materials that exhibit exceptional properties for diverse applications in areas such as heterogeneous catalysis, energy storage and conversion, and bio-medical applications, among others. Efforts have been devoted to produce millimeter-scale LDH structures for direct integration into functional devices. However, the controlled synthesis of self-supported continuous LDH materials with hierarchical structuring up to the millimeter scale through a straightforward one-pot reaction method remains unaddressed. Herein, it is shown that millimeter-scale self-supported LDH structures can be produced by means of a continuous flow microfluidic device in a rapid and reproducible one-pot process. Additionally, the microfluidic approach not only allows for an "on-the-fly" formation of unprecedented LDH composite structures, but also for the seamless integration of millimeter-scale LDH structures into functional devices. This method holds the potential to unlock the integrability of these materials, maintaining their performance and functionality, while diverging from conventional techniques like pelletization and densification that often compromise these aspects. This strategy will enable exciting advancements in LDH performance and functionality.

Tailored Design of a Water-Based Nanoreactor Technology for Producing Processable Sub-40 Nm 3D COF Nanoparticles at Atmospheric Conditions.

Covalent organic frameworks (COFs) are crystalline materials with intrinsic porosity that offer a wide range of potential applications spanning diverse fields. Yet, the main goal in the COF research area is to achieve the most stable thermodynamic product while simultaneously targeting the desired size and structure crucial for enabling specific functions. While significant progress is made in the synthesis and processing of 2D COFs, the development of processable 3D COF nanocrystals remains challenging. Here, a water-based nanoreactor technology for producing processable sub-40 nm 3D COF nanoparticles at ambient conditions is presented. Significantly, this technology not only improves the processability of the synthesized 3D COF, but also unveils exciting possibilities for their utilization in previously unexplored domains, such as nano/microrobotics and biomedicine, which are limited by larger crystallites.

The magnetopyroelectric effect: heat-mediated magnetoelectricity in magnetic nanoparticle-ferroelectric polymer composites.

Magnetoelectricity enables a solid-state material to generate electricity under magnetic fields. Most magnetoelectric composites are developed through a strain-mediated route by coupling piezoelectric and magnetostrictive phases. However, the limited availability of high-performance magnetostrictive components has become a constraint for the development of novel magnetoelectric materials. Here, we demonstrate that nanostructured composites of magnetic and pyroelectric materials can generate electrical output, a phenomenon we refer to as the magnetopyroelectric (MPE) effect, which is analogous to the magnetoelectric effect in strain-mediated composite multiferroics. Our composite consists of magnetic iron oxide nanoparticles (IONPs) dispersed in a ferroelectric (and also pyroelectric) poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) matrix. Under a high-frequency low-magnitude alternating magnetic field, the IONPs generate heat through hysteresis loss, which stimulates the depolarization process of the pyroelectric polymer. This magnetopyroelectric approach creates a new opportunity to develop magnetoelectric materials for a wide range of applications.

In Situ Sprayed Nanovaccine Suppressing Exosomal PD-L1 by Golgi Apparatus Disorganization for Postsurgical Melanoma Immunotherapy.

The anti-PD-L1 immunotherapy has shown promise in treating cancer. However, certain patients with metastatic cancer have low response and high relapse rates. A main reason is systemic immunosuppression caused by exosomal PD-L1, which can circulate in the body and inhibit T cell functions. Here, we show that Golgi apparatus-Pd-l1-/- exosome hybrid membrane coated nanoparticles (GENPs) can significantly reduce the secretion of PD-L1. The GENPs can accumulate in tumors through homotypic targeting and effectively deliver retinoic acid, inducing disorganization of the Golgi apparatus and a sequence of intracellular events including alteration of endoplasmic reticulum (ER)-to-Golgi trafficking and subsequent ER stress, which finally disrupts the PD-L1 production and the release of exosomes. Furthermore, GENPs could mimic exosomes to access draining lymph nodes. The membrane antigen of PD-l1-/- exosome on GENPs can activate T cells through a vaccine-like effect, strongly promoting systemic immune responses. By combining GENPs with anti-PD-L1 treatment in the sprayable in situ hydrogel, we have successfully realized a low recurrence rate and substantially extended survival periods in mice models with incomplete metastatic melanoma resection.

Shape-memory effect in twisted ferroic nanocomposites.

The shape recovery ability of shape-memory alloys vanishes below a critical size (~50 nm), which prevents their practical applications at the nanoscale. In contrast, ferroic materials, even when scaled down to dimensions of a few nanometers, exhibit actuation strain through domain switching, though the generated strain is modest (~1%). Here, we develop freestanding twisted architectures of nanoscale ferroic oxides showing shape-memory effect with a giant recoverable strain (>8%). The twisted geometrical design amplifies the strain generated during ferroelectric domain switching, which cannot be achieved in bulk ceramics or substrate-bonded thin films. The twisted ferroic nanocomposites allow us to overcome the size limitations in traditional shape-memory alloys and open new avenues in engineering large-stroke shape-memory materials for small-scale actuating devices such as nanorobots and artificial muscle fibrils.

Multi-target cell therapy using a magnetoelectric microscale biorobot for targeted delivery and selective differentiation of SH-SY5Y cells via magnetically driven cell stamping.

Cell therapy refers to a treatment that involves the delivery of cells or cellular material by means of injection, grafting, or implantation in order to replace damaged tissue and restore its function, or to aid the body in fighting disease. However, limitations include poor targeting delivery and low therapeutic efficacy due to low cell survival. Hence, novel approaches are required to increase cell delivery efficiency and enhance therapeutic efficacy via selective cell differentiation at target areas. Here, we present a stamping magnetoelectric microscale biorobot (SMMB) consisting of neuron-like cell spheroids loaded with magnetoelectric nanoparticles. The SMMB enables not only effective targeted delivery of cells to multiple target areas (via minimally invasive stamping employing magnetic actuation) but also facilitates selective neuronal differentiation via magnetoelectric (ME) stimulation. This ensures rapid colonization and enhances efficacy. SMMBs were fabricated using SH-SY5Y cells. Magnetoelectric nanoparticles for ME stimulation responded to an alternating magnetic field that ensured targeted cell differentiation. Multi-target cell therapy facilitated the targeted delivery and selective differentiation of SH-SY5Y cells to multiple regions using a single SMMB with rotating and alternating magnetic fields for delivery and ME stimulation. This promising tool may overcome the limitations of existing cell therapy for neurodegenerative diseases.

MoSBOTs: Magnetically Driven Biotemplated MoS2 -Based Microrobots for Biomedical Applications.

2D layered molybdenum disulfide (MoS2 ) nanomaterials are a promising platform for biomedical applications, particularly due to its high biocompatibility characteristics, mechanical and electrical properties, and flexible functionalization. Additionally, the bandgap of MoS2 can be engineered to absorb light over a wide range of wavelengths, which can then be transformed into local heat for applications in photothermal tissue ablation and regeneration. However, limitations such as poor stability of aqueous dispersions and low accumulation in affected tissues impair the full realization of MoS2 for biomedical applications. To overcome such challenges, herein, multifunctional MoS2 -based magnetic helical microrobots (MoSBOTs) using cyanobacterium Spirulina platensis are proposed as biotemplate for therapeutic and biorecognition applications. The cytocompatible microrobots combine remote magnetic navigation with MoS2 photothermal activity under near-infrared irradiation. The resulting photoabsorbent features of the MoSBOTs are exploited for targeted photothermal ablation of cancer cells and on-the-fly biorecognition in minimally invasive oncotherapy applications. The proposed multi-therapeutic MoSBOTs hold considerable potential for a myriad of cancer treatment and diagnostic-related applications, circumventing current challenges of ablative procedures.

Magnetoelectric Effect in Hydrogen Harvesting: Magnetic Field as a Trigger of Catalytic Reactions.

Magnetic fields have been regarded as an additional stimulus for electro- and photocatalytic reactions, but not as a direct trigger for catalytic processes. Multiferroic/magnetoelectric materials, whose electrical polarization and surface charges can be magnetically altered, are especially suitable for triggering and control of catalytic reactions solely with magnetic fields. Here, it is demonstrated that magnetic fields can be employed as an independent input energy source for hydrogen harvesting by means of the magnetoelectric effect. Composite multiferroic CoFe2 O4 -BiFeO3 core-shell nanoparticles act as catalysts for the hydrogen evolution reaction (HER), which is triggered when an alternating magnetic field is applied to an aqueous dispersion of the magnetoelectric nanocatalysts. Based on density functional calculations, it is proposed that the hydrogen evolution is driven by changes in the ferroelectric polarization direction of BiFeO3 caused by the magnetoelectric coupling. It is believed that the findings will open new avenues toward magnetically induced renewable energy harvesting.

Thermoset Shape Memory Polymer Variable Stiffness 4D Robotic Catheters.

Variable stiffness catheters are typically composed of an encapsulated core. The core is usually composed of a low melting point alloy (LMPA) or a thermoplastic polymer (TP). In both cases, there is a need to encapsulate the core with an elastic material. This imposes a limit to the volume of variable stiffness (VS) material and limits miniaturization. This paper proposes a new approach that relies on the use of thermosetting materials. The variable stiffness catheter (VSC) proposed in this work eliminates the necessity for an encapsulation layer and is made of a unique biocompatible thermoset polymer with an embedded heating system. This significantly reduces the final diameter, improves manufacturability, and increases safety in the event of complications. The device can be scaled to sub-millimeter dimensions, while maintaining a high stiffness change. In addition, integration into a magnetic actuation system allows for precise actuation of one or multiple tools.

Biodegradable Small-Scale Swimmers for Biomedical Applications.

Most forms of biomatter are ephemeral, which means they transform or deteriorate after a certain time. From this perspective, implantable healthcare devices designed for temporary treatments should exhibit the ability to degrade and either blend in with healthy tissues, or be cleared from the body with minimal disruption after accomplishing their designated tasks. This topic is currently being investigated in the field of biomedical micro- and nanoswimmers. These tiny devices have the ability to move through fluids by converting physical or chemical energy into motion. Several architectures of these devices have been designed to mimic the motion strategies of nature's motile microorganisms and cells. Due to their motion abilities, these devices have been proposed as minimally invasive tools for precision healthcare applications. Hence, a natural progression in this field is to produce motile structures that can adopt, or even surpass, similar transient features as biological systems. The fate of small-scale swimmers after accomplishing their therapeutic mission is critical for the successful translation of small-scale swimmers' technologies into clinical applications. In this review, recent research efforts are summarized on the topic of biodegradable micro- and nanoswimmers for biomedical applications, with a focus on targeted therapeutic delivery.

Powering and Fabrication of Small-Scale Robotics Systems.

PURPOSE OF REVIEW: The increasing number of contributions in the field of small-scale robotics is significantly associated with the progress in material science and process engineering during the last half century. With the objective of integrating the most optimal materials for the propulsion of these motile micro- and nanosystems, several manufacturing strategies have been adopted or specifically developed. This brief review covers some recent advances in materials and fabrication of small-scale robots with a focus on the materials serving as components for their motion and actuation. RECENT FINDINGS: Integration of a wealth of materials is now possible in several micro- and nanorobotic designs owing to the advances in micro- and nanofabrication and chemical synthesis. Regarding light-driven swimmers, novel photocatalytic materials and deformable liquid crystal elastomers have been recently reported. Acoustic swimmers are also gaining attention, with several prominent examples of acoustic bubble-based 3D swimmers being recently reported. Magnetic micro- and nanorobots are increasingly investigated for their prospective use in biomedical applications. The adoption of different materials and novel fabrication strategies based on 3D printing, template-assisted electrodeposition, or electrospinning is briefly discussed. SUMMARY: A brief review on fabrication and powering of small-scale robotics is presented. First, a concise introduction to the world of small-scale robotics and their propulsion by means of magnetic fields, ultrasound, and light is provided. Recent examples of materials and fabrication methodologies for the realization of these devices follow thereafter.

CANDYBOTS: A New Generation of 3D-Printed Sugar-Based Transient Small-Scale Robots.

Sugars are ubiquitous in food, and are among the main sources of energy for almost all forms of life. Sugars can also form structural building blocks such as cellulose in plants. Because of their inherent degradability and biocompatibility characteristics, sugars are compelling materials for transient devices. Here, an additive manufacturing approach for the production of magnetic sugar-based composites is introduced. First, it is shown that sugar-based 3D architectures can be 3D printed by selective laser sintering. This method enables not only the caramelization chemistry but also the mechanical properties of the sugar architectures to be adjusted by varying the laser energy. It is also demonstrated that mixtures of sugar and magnetic particles can be processed as 3D composites. As a proof of concept, a sugar-based millimeter-scale helical swimmer, which is capable of corkscrew motion in a solution with a viscosity comparable to those of biological fluids, is fabricated. The millirobot quickly dissolves in water, while being manipulated through magnetic fields. The present fabrication method can pave the way to a new generation of transient sugar-based small-scale robots for minimally invasive procedures. Due to their rapid dissolution, sugars can be used as an intermediate step for transporting swarms of particles to specific target locations.

Metal-Organic Frameworks in Motion.

During the last two decades, engineering motion with small-scale matter has received much attention in several areas of research, ranging from supramolecular chemistry and colloidal science to robotics and automation. The numerous discoveries and innovative concepts realized in motile micro- and nanostructures have converged in the field of small-scale swimmers. These man-made micro- and nanomachines can move in fluids by transforming different forms of energy to mechanical motion. Recently, metal-organic frameworks (MOFs), which are crystalline coordination polymers with high porosity, have been proposed as key building blocks in several small-scale swimmer designs. These materials possess the required features for motile micro- and nanodevices, such as high cargo-loading capacity, biodegradability, biocompatibility, and stimuli-responsiveness. In this review, we take a journey through the major breakthroughs and milestones realized in the area of MOF-based small-scale swimmers. First, a brief introduction to the field of small-scale swimmers is provided. Next, we review different strategies that have been reported for imparting motion to MOFs. Finally, we emphasize the incorporation of molecular machines into the MOF's architecture as the means to create highly integrated small-scale swimmers. The strategies and developments explored in this review pave the way toward the use of motile MOFs for a variety of applications in the fields of biomedicine, environmental remediation, and on-the-fly chemistry.

Biodegradable Metal-Organic Framework-Based Microrobots (MOFBOTs).

Microrobots and metal-organic frameworks (MOFs) have been identified as promising carriers for drug delivery applications. While clinical applications of microrobots are limited by their low drug loading efficiencies and the poor degradability of the materials used for their fabrication, MOFs lack motility and targeted drug delivery capabilities. The combination of these two fields marks the beginning of a new era; MOF-based small-scale robots (MOFBOTs) for biomedical applications. Yet, biodegradability is a major hurdle in the field of micro- and nanoswimmers including small-scale robots. Here, a highly integrated MOFBOT that is able to realize magnetic locomotion, drug delivery, and selective degradation in cell cultures is reported for the first time. The MOF used in the investigations does not only allow a superior loading of chemotherapeutic drugs and their controlled release via a pH-responsive degradation but it also enables the controlled locomotion of enzymatically biodegradable gelatin-based helical microrobots under magnetic fields. The degradation of the integrated MOFBOT is observed after two weeks, when all its components fully degrade. Additionally, drug delivery studies performed in cancer cell cultures show reduced viability upon delivery of Doxorubicin within short time frames. This MOFBOT system opens new avenues for highly integrated fully biodegradable small-scale robots.