A light‐activated hypoxia‐responsive conjugated polymer‐based nanocarrier is developed for efficiently producing singlet oxygen (1O2) and inducing hypoxia to promote release of its cargoes in tumor ...cells, leading to enhanced antitumor efficacy. This dual‐responsive nanocarrier provides an innovative design guideline for enhancing traditional photodynamic therapeutic efficacy integrated with a controlled drug‐release modality.
Neurodegenerative diseases generally result in irreversible neuronal damage and neuronal death. Cell therapy shows promise as a potential treatment for these diseases. However, the therapeutic ...targeted delivery of these cells and the in situ provision of a suitable microenvironment for their differentiation into functional neuronal networks remain challenging. A highly integrated multifunctional soft helical microswimmer featuring targeted neuronal cell delivery, on‐demand localized wireless neuronal electrostimulation, and post‐delivery enzymatic degradation is introduced. The helical soft body of the microswimmer is fabricated by two‐photon lithography of the photocurable gelatin–methacryloyl (GelMA)‐based hydrogel. The helical body is then impregnated with composite multiferroic nanoparticles displaying magnetoelectric features (MENPs). While the soft GelMA hydrogel chassis supports the cell growth, and is degraded by enzymes secreted by cells, the MENPs allow for the magnetic transportation of the bioactive chassis, and act as magnetically mediated electrostimulators of neuron‐like cells. The unique combination of the materials makes these microswimmers highly integrated devices that fulfill several requirements for their future translation to clinical applications, such as cargo delivery, cell stimulation, and biodegradability. The authors envision that these devices will inspire new avenues for targeted cell therapies for traumatic injuries and diseases in the central nervous system.
Biodegradable soft magnetoelectric microswimmers are fabricated using a 3D‐printing technique. These microswimmers can perform targeted delivery of neuron‐like cells and induce neuronal differentiation of these cells under different magnetic stimulation modes. This combinatorial technique is a significant step towards highly integrated microrobots, and may open up new avenues for cell therapies.
The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid‐brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels ...in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.
Degeneration of dopaminergic neurons is a most common age‐related disorder in the central nervous system. A break‐through idea using electromagnetized nanoparticles to mediate neural plasticity and recover the functions of degenerative dopaminergic neurons in the midbrain of a Parkinson's disease animal model is conceived. A significant advance in remote and regenerative cell therapy of the neurodegenerative diseases is thus provided.
Anaerobic bacteria, such as Clostridium and Salmonella, can selectively invade and colonize in tumor hypoxic regions (THRs) and deliver therapeutic products to destroy cancer cells. Herein, we ...present an anaerobe nanovesicle mimic that can not only be activated in THRs but also induce hypoxia in tumors by themselves. Moreover, inspired by the oxygen metabolism of anaerobes, we construct a light‐induced hypoxia‐responsive modality to promote dissociation of vehicles and activation of bioreductive prodrugs simultaneously. In vitro and in vivo experiments indicate that this anaerobe‐inspired nanovesicle can efficiently induce apoptotic cell death and significantly inhibit tumor growth. Our work provides a new strategy for engineering stimuli‐responsive drug delivery systems in a bioinspired and synergistic fashion.
A biomimetic vesicle mimics the natural mode of tumor targeting and therapeutic drug delivery of anaerobic bacteria. The nanovesicle is stable in cells with normal physiological redox and oxygen balance; however, once disrupted by external light stimuli, it shows dual synergistic anticancer actions with enhanced therapeutic efficacy.
Abstract
With speeding up development of 5 G chips, high-efficient thermal structure and precise management of tremendous heat becomes a substantial challenge to the power-hungry electronics. Here, ...we demonstrate an interpenetrating architecture of electrocaloric polymer with highly thermally conductive pathways that achieves a 240% increase in the electrocaloric performance and a 300% enhancement in the thermal conductivity of the polymer. A scaled-up version of the device prototype for a single heat spot cooling of 5 G chip is fabricated utilizing this electrocaloric composite and electromagnetic actuation. The continuous three-dimensional (3-D) thermal conductive network embedded in the polymer acts as nucleation sites of the ordered dipoles under applied electric field, efficiently collects thermal energy at the hot-spots arising from field-driven dipolar entropy change, and opens up the high-speed conduction path of phonons. The synergy of two components, thus, tackles the challenge of sluggish heat dissipation of the electroactive polymers and their contact interfaces with low thermal conductivity, and more importantly, significantly reduces the electric energy for switching the dipolar states during the electrocaloric cycles, and increases the manipulable entropy at the low fields. Such a feasible solution is inevitable to the precisely fixed-point thermal management of next-generation smart microelectronic devices.
Ferroelectric polymers are of interest as most promising electroactive materials. Flexible transducers from ferroelectric polymer thin film with underneath semiconducting polymer active layer for ...high sensitive and versatile detection of physiological signals are described. When attached directly on the wrist, the flexible transducers can distinguish the transient pulse waves non‐invasively and in situ, due to their fast response (milliseconds) and high sensitivity (down to several Pascal) to instantaneous change of blood pressure. High‐resolution picture of one pulse wave is available to provide two most common parameters for arterial stiffness diagnosis. The transducers are also suitable for dynamic recognizing physiological signals under both physical exercise and medicine treatment, demonstrating their enormous potential for warning the risk of cardiovascular disease, and evaluating the efficacy of heart medicines. The transducers are easy to carry around with an operating voltage of 1 V and the power consumption less than 1 μW. Thus, they are valuable for applications like electronic skin and mobile health monitoring.
Portable devices for diagnosis of cardiovascular system: A simple yet efficient and low‐cost method can fabricate a wearable transducer for non‐invasive and dynamic diagnosis of cardiovascular system by using smart dielectric polymer poly(vinylidene fluoride‐trifluoroethylene‐chlorofluoroethylene). The transducer has low power consumption and is facile to integrate into portable devices for remote detecting warning signals of heart attacks and assessing efficiency of heart drugs.
Wireless micro- and nanorobots are biomedical devices with a potential use in high-precision minimally invasive therapies. Here, a highly integrated multifunctional soft microrobot is developed for ...targeted cell therapy applications, featuring targeted cell transportation and induced cell differentiation. The micromachines are made of composites consisting of a soft piezoelectric polymer matrix in which magnetic nanoparticles are dispersed. The magnetic nanoparticles serve as the component for the device's magnetic actuation, while the piezoelectric polymer acts as both a steerable scaffold and an acoustically responsive cell electrostimulation platform. With the application of a rotating magnetic field, the microrobots swim in a corkscrew motion in different liquid environments that mimic human body fluids. When the swimmers are subjected to acoustic waves, their piezoelectric body is electrically polarized which induces cell differentiation of neuron-like PC12 cells loaded on the swimmers surface. This combinatorial technique may open up new avenues for bioelectronic therapies.
Wireless piezoelectric microrobots are biomedical devices with a potential use in high-precision minimally invasive therapies.
Ferroelectric vinylidene fluoride‐trifluoroethylene copolymer P(VDF‐TrFE) free‐standing ultrahigh density (≈75 Gb inch−2) nanodot arrays are successfully fabricated through a facile, high‐throughput, ...and cost‐effective nano‐imprinting method using disposable anodic aluminum oxide with orderly arranged nanometer‐scale pores as molds. The nanodots show a large‐area smooth surface morphology, and the piezoresponse in each nanodot is strong and uniform. The preferred orientation of the copolymer chains in the nanodot arrays is favorable for polarization switching of single nanodots. The ferroelectric polymer memory prototype can be operated by a few volts with high writing/erasing speed, which comply with the requirements of integrated circuit. This approach provides a way of directly writing nanometer electronic features in two dimensions by piezoresponse force microscopy probe based technology, which is attractive for high density data storage.
Ferroelectric polymer P(VDF‐TrFE) free‐standing nanodot arrays with ultrahigh data storage density are fabricated through nano‐imprinting. The preferred orientation of the copolymer chains in the nanodot arrays is favorable for polarization switching of single nanodots. This approach allows nanometer electronic features to be written directly in two dimensions by piezoresponse force microscopy probe based technology.
A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive ...oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2‐deoxy‐glucose (2‐DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2‐DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS‐sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light‐induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.
A multimodal cancer therapeutic nano‐platform. It synergistically regulates tumor microenvironment by introducing reactive oxygen species (ROS) and endoplasmic reticulum stress to promote the efficiencies of photodynamic therapy and chemotherapy. The nanoplatform combines the advantages of ROS‐sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under endoplasmic reticulum stress, light‐induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability.
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