Near-infrared Stimulation Research Articles

Erratum] Brain Imaging and neurostimulation in health and disorders: status report

INTRODUCTION: Despite being considered least important for clinical practice in the pyramid of evidence for recommendations, sometimes scientists' expert opinions could help to better understand the summarization of updated publications. OBJECTIVE: To provide a major summarized update about brain imaging and stimulation of the nervous system in health and disease. METHODS: Comprehensive review developed by experts in each subarea of knowledge in neuroimaging and non-invasive stimulation of the nervous system. A team of researchers and clinic experts was invited to present an update on their area of expertise. RESULTS: In basics on brain imaging techniques, we approach general and quantitative electroencephalography, functional magnetic resonance imaging, functional near-infrared spectroscopy, and experimental paradigms in brain imaging studies. Were included associations between transcranial magnetic stimulation and electromyography, electroencephalography, and functional near-infrared stimulation to evaluate brain activity. Furthermore, we showed several actualized central and peripheral neuromodulation techniques. And finally, we presented different clinical and performance uses of non-invasive neuromodulation. CONCLUSION: To our knowledge, this is a major summarized and concentrated update about brain imaging and stimulation that can benefit neuroscience researchers and clinicians from different levels of experience.

NIR Enhanced pH-Responsive Microneedles for Synergetic Therapy of Melanoma.

Melanoma has emerged as a significant threat to human life and health. Microneedle (MN)-mediated transdermal drug delivery (TDD) has garnered attention in melanoma treatment for bypassing the first-pass effect. However, the propensity of melanoma to metastasize presents substantial challenges for MN mediated local treatment. Developing systemic therapies, such as immunotherapy in combination with TDD, is crucial for achieving effective melanoma treatment. Herein, a polyvinyl alcohol (PVA) MN-mediated multifunctional TDD system, designated MN@PDA@1-MT/CUR/DOX@HA (MN@PMCDH), was developed for synergetic chemotherapy/photothermal/immunotherapy of melanoma. PMCDH nanomedicines penetrate deep skin layers through MNs, accumulate at tumor sites guided by hyaluronic acid (HA), and selectively release drugs in response to the acidic tumor microenvironment and near-infrared (NIR) stimulation. Released curcumin (CUR) significantly enhances the efficacy of photothermal therapy (PTT) and chemotherapy, as well as improves the induction of immunogenic cell death (ICD) by increasing melanoma sensitivity to polydopamine (PDA)-mediated photothermal effects and doxorubicin (DOX). Moreover, the incorporation of 1-methyltryptophan (1-MT) to reverse the tumor immunosuppressive microenvironment can further enhance the effects of immunotherapy. In vitro studies revealed that the MN@PMCDH system can effectively induce ICD and inhibit tumor cell growth. Additionally, remarkable deep tumor cell inhibition effects are also achieved in 3D tumor models.

Remote neurostimulation through an endogenous ion channel using a near-infrared light-activatable nanoagonist.

The development of noninvasive approaches to precisely control neural activity in mammals is highly desirable. Here, we used the ion channel transient receptor potential ankyrin-repeat 1 (TRPA1) as a proof of principle, demonstrating remote near-infrared (NIR) activation of endogenous neuronal channels in mice through an engineered nanoagonist. This achievement enables specific neurostimulation in nongenetically modified mice. Initially, target-based screening identified flavins as photopharmacological agonists, allowing for the photoactivation of TRPA1 in sensory neurons upon ultraviolet A/blue light illumination. Subsequently, upconversion nanoparticles (UCNPs) were customized with an emission spectrum aligned to flavin absorption and conjugated with flavin adenine dinucleotide, creating a nanoagonist capable of NIR activation of TRPA1. Following the intrathecal injection of the nanoagonist, noninvasive NIR stimulation allows precise bidirectional control of nociception in mice through remote activation of spinal TRPA1. This study demonstrates a noninvasive NIR neurostimulation method with the potential for adaptation to various endogenous ion channels and neural processes by combining photochemical toolboxes with customized UCNPs.

Plasmonic nanozyme Cu3P with significantly enhanced peroxidase-like activity for Cr (VI) colorimetric detection

Plasmonic nanozymes with both plasmonic and biocatalytic properties stand out due to their distinctive localized surface plasmon resonance (LSPR) feature and adjustable catalytic activity, while the enhancement effect of present reported plasmon excitation remains relatively low. Here, a plasmonic nanozyme of Cu3P nanoparticles (Cu3P NPs) with LSPR characteristics and intrinsic peroxidase (POD)-like activity was prepared via simple gas-solid reaction strategy, which presents significantly enhanced POD-like activity under plasmon stimulation than that without LSPR excitation, with catalytic constants for TMB and H2O2 83 and 127 times higher than those without LSPR excitation respectively. On the one hand, the Cu3P plasmonic nanozyme generated abundant high-energy hot carriers under near-infrared (NIR) stimulation to promote cracking of H2O2 to produce plentiful reactive oxide species (ROS); on the other hand, the LSPR-induced photothermal effect on Cu3P plasmonic nanozyme greatly improves the reaction kinetics, thus making a significantly boosts POD-like activity. According to the excellent POD-like activity of Cu3P plasmonic nanozyme and 8-hydroxyquinoline (8-HQ)-mediated chromaticity switch, a highly sensitive Cr (VI) chrominance sensing platform was developed with a detection limit of 9.6 nM within a range from 0.01 to 20 μM. This study spotlights the high utilization efficiency of plasmon stimulation for enzyme-like activity tuning.

Photothermal hydrogels for infection control and tissue regeneration.

In this review, we report investigating photothermal hydrogels, innovative biomedical materials designed for infection control and tissue regeneration. These hydrogels exhibit responsiveness to near-infrared (NIR) stimulation, altering their structure and properties, which is pivotal for medical applications. Photothermal hydrogels have emerged as a significant advancement in medical materials, harnessing photothermal agents (PTAs) to respond to NIR light. This responsiveness is crucial for controlling infections and promoting tissue healing. We discuss three construction methods for preparing photothermal hydrogels, emphasizing their design and synthesis, which incorporate PTAs to achieve the desired photothermal effects. The application of these hydrogels demonstrates enhanced infection control and tissue regeneration, supported by their unique photothermal properties. Although research progress in photothermal hydrogels is promising, challenges remain. We address these issues and explore future directions to enhance their therapeutic potential.

Microenvironment with NIR-Controlled ROS and Mechanical Tensions for Manipulating Cell Activities in Wound Healing.

The extracellular matrix (ECM) orchestrates cell behavior and tissue regeneration by modulating biochemical and mechanical signals. Manipulating cell-material interactions is crucial for leveraging biomaterials to regulate cell functions. Yet, integrating multiple cues in a single material remains a challenge. Here, near-infrared (NIR)-controlled multifunctional hydrogel platforms, named PIC/CM@NPs, are introduced to dictate fibroblast behavior during wound healing by tuning the matrix oxidative stress and mechanical tensions. PIC/CM@NPs are prepared through cell adhesion-medicated assembly of collagen-like polyisocyanide (PIC) polymers and cell-membrane-coated conjugated polymer nanoparticles (CM@NPs), which closely mimic the fibrous structure and nonlinear mechanics of ECM. Upon NIR stimulation, PIC/CM@NPs composites enhance fibroblast cell proliferation, migration, cytokine production, and myofibroblast activation, crucial for wound closure. Moreover, they exhibit effective and toxin removal antibacterial properties, reducing inflammation. This multifunctional approach accelerates healing by 95%, highlighting the importance of integrating biochemical and biophysical cues in the biomaterial design for advanced tissue regeneration.

Engineering Dual CO2- and Photothermal-Responsive Membranes for Switchable Double Emulsion Separation.

Stimulus-responsive membranes demonstrate promising applications in switchable oil/water emulsion separations. However, they are unsuitable for the treatment of double emulsions like oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) emulsions. For efficient separation of these complicated emulsions, fine control over the wettability, response time, and aperture structure of the membrane is required. Herein, dual-coated fibers consisting of primary photothermal-responsive and secondary CO2-responsive coatings are prepared by two steps. Automated weaving of these fibers produces membranes with photothermal- and CO2-responsive characteristics and narrow pore size distributions. These membranes exhibit fast switching wettability between superhydrophilicity (under CO2 stimulation) and high hydrophobicity (under near-infrared stimulation), achieving on-demand separation of various O/W/O and W/O/W emulsions with separation efficiencies exceeding 99.6%. Two-dimensional low-field nuclear magnetic resonance and correlated spectra technique are used to clarify the underlying mechanism of switchable double emulsion separation. The approach can effectively address the challenges associated with the use of stimulus-responsive membranes for double emulsion separation and facilitate the industrial application of these membranes.

Transcranial near-infrared stimulation of the left DLPFC relieved anxiety: a randomized, double-blind, sham-controlled study Transcranial near-infrared stimulation of the left DLPFC relieved anxiety. A randomized, double-blind, sham-controlled study

Transcranial near-infrared stimulation of the left DLPFC relieved anxiety: a randomized, double-blind, sham-controlled study Transcranial near-infrared stimulation of the left DLPFC relieved anxiety. A randomized, double-blind, sham-controlled study

Photothermal effects of supra-CNDs@GelMA composite hydrogels under near-infrared stimulation

In this study, supra-CNDs@GelMA composite hydrogel dressings for the photothermal treatment of melanoma were successfully developed. The prepared supra-CNDs (supra-carbon nanodots) exhibited remarkable photothermal properties, with a photothermal conversion efficiency of 55.29 % (47.12 %) under 730 nm (808 nm) laser irradiation, which is a promising material for photothermal reagents. The integrated GelMA (gelatine methacryloyl hydrogel) further enhanced the photothermal effects of the supra-CNDs@GelMA composite hydrogels and also shortened the exposure time, which could rapidly reach 50 ℃ within 70 s under 808 nm laser irradiation (1 W/cm2). Additionally, the thermal conductivity of the composite hydrogels was investigated at a laser spot diameter of 2 mm. Moreover, the supra-CNDs@GelMA composite hydrogels exhibited good biocompatibility and excellent photothermal ablation of melanoma cells. These findings demonstrate the potential of the supra-CNDs@GelMA composite hydrogels as dressings for the photothermal treatment of skin cancers.

Brain Imaging and neurostimulation in health and disorders: status report

INTRODUCTION: Despite being considered least important for clinical practice in the pyramid of evidence for recommendations, sometimes scientists' expert opinions could help to better understand the summarization of updated publications. OBJECTIVE: To provide a major summarized update about brain imaging and stimulation of the nervous system in health and disease. METHODS: Comprehensive review developed by experts in each subarea of knowledge in neuroimaging and non-invasive stimulation of the nervous system. A team of researchers and clinic experts was invited to present an update on their area of expertise. RESULTS: In basics on brain imaging techniques, we approach general and quantitative electroencephalography, functional magnetic resonance imaging, functional near-infrared spectroscopy, and experimental paradigms in brain imaging studies. Were included associations between transcranial magnetic stimulation and electromyography, electroencephalography, and functional near-infrared stimulation to evaluate brain activity. Furthermore, we showed several actualized central and peripheral neuromodulation techniques. And finally, we presented different clinical and performance uses of non-invasive neuromodulation. CONCLUSION: To our knowledge, this is a major summarized and concentrated update about brain imaging and stimulation that can benefit neuroscience researchers and clinicians from different levels of experience.

820-nm Transcranial near-infrared stimulation on the left DLPFC relieved anxiety: A randomized, double-blind, sham-controlled study

ObjectiveGeneralized anxiety disorder (GAD) is a chronic mood disease associated with abnormal brain network connections, including decreased activity in the left dorsolateral prefrontal cortex (DLPFC). Cortical excitability can be increased with 820-nm transcranial near-infrared stimulation (tNIRS), while transcranial magnetic stimulation with electroencephalography (TMS-EEG) can help evaluate time-varying brain network connectivity. A randomized, double-blind, sham-controlled trial was conducted to assess the efficacy of tNIRS on the left DLPFC and the impact on time-varying brain network connections in GAD patients. MethodsA total of 36 GAD patients were randomized to receive active or sham tNIRS for 2 weeks. Clinical psychological scales were assessed before, after, and at the 2-, 4-, and 8-week follow-ups. TMS-EEG was performed for 20 min before and immediately after tNIRS treatment. The healthy controls did not receive tNIRS and only had TMS-EEG data collected once in the resting state. ResultsThe Hamilton Anxiety Scale (HAMA) scores of the active stimulation group decreased post-treatment compared with the sham group (P = 0.021). The HAMA scores of the active stimulation group at the 2-, 4-, and 8-week follow-up assessments were lower than those before treatment (P < 0.05). The time-varying EEG network pattern showed an information outflow from the left DLPFC and the left posterior temporal region after active treatment. ConclusionHerein, 820-nm tNIRS targeting the left DLPFC had significant positive effects on therapy for GAD that lasted at least 2 months. tNIRS may reverse the abnormality of time-varying brain network connections in GAD.

BMP-2@PNH-TA hydrogel with osteogenic and antibacterial properties for integrated photothermal therapy

Progress toward developing next-generation biomaterials applied in complex bone defect is expected to effectively integrate osteogenic and anti-bacteria capability. However, current biomaterials often achieve the two functions separately. Inspired by photothermal effect, exogenous light-induced thermal variations can efficiently facilitate bone regeneration and bacteria eradication. Here, a bioactive hydrogel BMP-2@PNH-TA with simultaneously osteogenic and anti-bacterial capacities is presented, which is based on the near infrared (NIR) induced photothermal effect to perform integrated photothermal therapy (PTT). In detail, photothermal effect and photothermal-controlled release of osteogenic and anti-bacterial factors through sponge-like effect could exert integrated influence on bone regeneration under complex situation. The composite hydrogel can mediate pro-osteogenesis under mild temperature and controlled release of BMP-2 and tannin in response to NIR stimulation with low power, while efficiently eradicate bacteria via controlled release of O-HACC and thermal effect with high power. The customized PTT strategy significantly shortened the duration time of bone regeneration up to almost 50% in rat cranial bone defect. It is anticipated that the concept of integrated PTT for bone regeneration will cast new insights into developing high-performance therapeutic strategy with combined biological functions.

Near-infrared light-responsive multifunctional hydrogel releasing peptide-functionalized gold nanorods sequentially for diabetic wound healing

Treatment for chronic diabetic wounds remains a clinical challenge. Wound healing process occurs in three phases: inflammation, proliferation and remodeling. Several factors including bacterial infection, decreased local angiogenesis and diminished blood supply delay wound healing. There is an urgent need to develop wound dressings with multiple biological effects for different stages of diabetic wound healing. Here, we develop a multifunctional hydrogel with two-stage sequential release upon near-infrared (NIR) stimulation, antibacterial activity and pro-angiogenic efficacy. This hydrogel consists of covalently crosslinked bilayer structure, with the lower thermoresponsive poly(N-isopropylacrylamide)/gelatin methacrylate (NG) layer and the upper highly stretchable alginate/polyacrylamide (AP) layer embedding different peptide-functionalized gold nanorods (AuNRs) in each layer. Antimicrobial peptide-functionalized AuNRs released from NG layer exert antibacterial effects. After NIR irradiation, the photothermal transition efficacy of AuNRs synergistically enhances bactericidal efficacy. The contraction of thermoresponsive layer also promotes the release of embedded cargos during early stage. The pro-angiogenic peptide-functionalized AuNRs released from AP layer promote angiogenesis and collagen deposition by accelerating fibroblast and endothelial cell proliferation, migration and tube formation during the subsequent healing phases. Therefore, the multifunctional hydrogel with effective antibacterial activity, pro-angiogenic efficacy and sequential release behaviors is a potential biomaterial for diabetic chronic wound healing.

Scalable Production of Biomedical Microparticles via High-Throughput Microfluidic Step Emulsification.

Drug microcarriers are widely used in disease treatment, and microfluidics is well established in the preparation of microcarrier particles. A proper design of the microfluidic platform toward scalable production of drug microcarriers can extend its application values in wound healing, where large numbers of microcarriers are required. Here, a microfluidic step emulsification method for the preparation of monodisperse droplets is presented. The droplet size depends primarily on the microchannel depth rather than flow rate, making the system robust for high-throughput production of droplets and hydrogel microparticles. Based on this platform, basic fibroblast growth factor (bFGF) is uniformly encapsulated in the microparticles, and black phosphorus (BP) is incorporated for controllable release via near-infrared (NIR) stimulation. The microparticles serve as drug carriers to be applied to the wound site, inducing angiogenesis and collagen deposition, thereby accelerating wound repair. These results indicate that the step emulsification technique provides a promising solution to scalable production of drug microcarriers for wound healing as well as tissue regeneration.

Bio-inspired Oxidative Stress Amplifier for Suppressing Cancer Metastasis and Imaging-Guided Combination Therapy

Antioxidant-defense systems of tumor cells protect them from oxidative damage and is strongly associated with tumor metastasis. In this work, a mussel-inspired multifunctional nanomedicine (ZS-MB@P) has been designed for inhibiting tumor growth and metastasis through amplified oxidative stress and photothermal/magnetothermal/photodynamic triple-combination therapy. This nanomedicine was fabricated via loading a silica shell on the magnetic nano-octahedrons [zinc-doped magnetic Fe3O4 nano-octahedrons] by encapsulating photosensitizer methylene blue (MB) and subsequently coating polydopamine (PDA) shells as "gatekeeper." The nanomedicine could realize photothermal therapy, photodynamic therapy, and magnetic hyperthermia after treatment with near-infrared (NIR) irradiation and applied magnetic field. Under pH and NIR stimulation, controlled amount of MB was released to produced exogenous reactive oxygen species. Noteworthy, PDA can amplify intracellular oxidative stress by depleting glutathione, thus inhibiting breast cancer metastasis effectively since oxidative stress is an important barrier to tumor metastasis. The outstanding ability to suppress tumor growth and metastasis was comprehensively assessed and validated both in vitro and in vivo. Moreover, the nanomedicine showed outstanding T2 magnetic resonance imaging for tracking the treatment process. Taken together, this work offers an innovative approach in the synergistic treatment of recalcitrant breast cancer.

Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.

K. Zheng et al. Gold-nanoparticle-based multistage drug delivery system for antitumor therapy

Nanoparticles can promote the accumulation of drugs in tumors. However, they find limited clinical applications because they cannot easily penetrate the stroma of cancer tissues, and it is difficult to control drug release. We developed a multiresponse multistage drug-delivery nanogel with improved tumor permeability and responsiveness to the tumor microenvironment for the controlled delivery of anticancer agents. For this purpose, ∼100 nm multistage drug delivery nanogels with pH, redox, near-infrared stimulation, and enzyme responsiveness were grown in situ using 20 nm gold nanoparticles (AuNPs) via an emulsion-aiding crosslinking technique with cysteine crosslinker. An alginate cysteine AuNP (ACA) nanocarrier can efficiently load the cationic drug doxorubicin (DOX) to produce a multistage drug delivery nanocarrier (DOX@ACA). DOX@ACA can maintain the slow release of DOX and reduce its toxicity. In cancer tissues, the high pH and reductase microenvironment combined with the in vitro delivery of alginate and near-infrared light drove drug release. The developed nanoparticles effectively inhibited cancer cells, and in vivo evaluations showed that they effectively enhanced antitumor activity while having negligible in vivo toxicity to major organs.

Upconverting nanoparticle-containing erythrocyte-sized hemoglobin microgels that generate heat, oxygen and reactive oxygen species for suppressing hypoxic tumors.

Inspired by erythrocytes that contain oxygen-carrying hemoglobin (Hb) and that exhibit photo-driven activity, we introduce homogenous-sized erythrocyte-like Hb microgel (μGel) systems (5–6 μm) that can (i) emit heat, (ii) supply oxygen, and (iii) generate reactive oxygen species (ROS; 1O2) in response to near-infrared (NIR) laser irradiation. Hb μGels consist of Hb, bovine serum albumin (BSA), chlorin e6 (Ce6) and erbium@lutetium upconverting nanoparticles (UCNPs; ∼35 nm) that effectively convert 808 nm NIR light to 660 nm visible light. These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species (1O2) from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity. Moreover, the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme (iron protoporphyrin IX) and display photothermal activity. By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation, it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect. These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.

Light-to-Heat Converting ECM-Mimetic Nanofiber Scaffolds for Neuronal Differentiation and Neurite Outgrowth Guidance.

The topological cues of fibrous scaffolds (in particular extracellular matrix (ECM)-mimetic nanofibers) have already proven to be a powerful tool for influencing neuronal morphology and behavior. Remote photothermal optical treatment provides additional opportunities for neuronal activity regulation. A combination of these approaches can provide “smart” 3D scaffolds for efficient axon guidance and neurite growth. In this study we propose two alternative approaches for obtaining biocompatible photothermal scaffolds: surface coating of nylon nanofibers with light-to-heat converting nanoparticles and nanoparticle incorporation inside the fibers. We have determined photoconversion efficiency of fibrous nanomaterials under near infrared (NIR) irradiation, as well as biocompatible photothermal treatment parameters. We also measured photo-induced intracellular heating upon contact of cells with a plasmonic surface. In the absence of NIR stimulation, our fibrous scaffolds with a fiber diameter of 100 nm induced an increase in the proportion of β3-tubulin positive cells, while thermal stimulation of neuroblastoma cells on nanoparticles-decorated scaffolds enhanced neurite outgrowth and promoted neuronal maturation. We demonstrate that contact guidance decorated fibers can stimulate directional growth of processes of differentiated neural cells. We studied the impact of nanoparticles on the surface of ECM-mimetic scaffolds on neurite elongation and axonal branching of rat hippocampal neurons, both as topographic cues and as local heat sources. We show that decorating the surface of nanofibers with nanoparticles does not affect the orientation of neurites, but leads to strong branching, an increase in the number of neurites per cell, and neurite elongation, which is independent of NIR stimulation. The effect of photothermal stimulation is most pronounced when cultivating neurons on nanofibers with incorporated nanoparticles, as compared to nanoparticle-coated fibers. The resulting light-to-heat converting 3D materials can be used as tools for controlled photothermal neuromodulation and as “smart” materials for reconstructive neurosurgery.

Fast-Response Bioinspired Near-Infrared Light-Driven Soft Robot Based on Two-Stage Deformation.

Herein, we report a remotely controlled soft robot employing a photoresponsive nanocomposite synthesized from liquid crystal elastomers (LCEs), high elastic form-stable phase change polymer (HEPCP), and multiwalled carbon nanotubes (MWCNTs). Possessing a two-stage deformation upon exposure to near-infrared (NIR) light, the LCE/HEPCP/MWCNT (LHM) nanocomposite allows the soft robot to exhibit an obvious, fast, and reversible shape change with low detection limitations. In addition to the deformation and bending of the LCE molecular chains itself, the HEPCP in the composite material can also be triggered by a reversible solid-liquid transition due to the temperature rise caused by MWCNTs, which further promotes the change of the LCE. In particular, the proposed photodriven LHM soft robot can bend up to 180° in 2 s upon NIR stimulation (320 mW, distance of 5 cm) and generate recoverable, dramatic, and sensitive deformation to execute various tasks including walking, twisting, and bending. With the capacity of imitating biological behaviors through remote control, the disruptive innovation developed here offers a promising path toward miniaturized untethered robotic systems.