With the rapid development of micro/nanomanufacturing technology, a variety of multifunctional micro/nanorobots have emerged. In particular, magnetic actuation‐based micro/nanorobots have attracted ...much interest due to their advantages of untethered contact, remote control, noninvasiveness, and high tissue‐penetrating capability. Various magnetic micro/nanorobots have been designed and applied in biomedicine, which indicates the great potential of clinical transformation. This article reviews the new advancements of engineering magnetic micro/nanorobots for versatile biomedical applications, ranging from targeted delivery, minimally invasive surgery, cellular and intracellular measurement, and intelligent sensing to detoxification and antibacterial applications. The controllability, visualization, and biosafety aspects of magnetically manipulated micro/nanorobots are summarized. In particular, the challenges being faced are discussed to outlook future prospective development.
Recent advancements of engineering magnetic micro/nanorobots in biomedicine are summarized. The synthesis methods, magnetic actuation systems, locomotion modes, and various monitoring modalities are introduced. The biomedical application progress of magnetic micro/nanorobots is highlighted, and the challenges being faced are discussed. Thus, promising opportunities for future development of magnetic micro/nanorobots in biomedical applications are provided.
Medical ultrasound device has been more and more widely used in the hospital and Its safety risk is significantly increased when failures occur. However, there is a lack of quantitative risk ...assessments of different types of failure modes for medical ultrasound device. This study utilizes a failure mode, effect and criticality analysis (FMECA) approach for quantitative risk evaluation of different failure modes for ultrasound devices.
The 4216 medical ultrasound device failure records at various hospitals were investigated. A failure mode and effect analysis method was developed for the quantitative evaluation of the risks of different failure modes. Visual correlation analysis was conducted for all categories to identify the causes of various failure modes. Based on the severity, occurrence and detectability of the failure causes determined, the risk priority number (RPN) for each failure mode was back-calculated through the obtained tracking diagram.
The failure modes of unclear images, unable to power on and dark shadows on an image had the highest RPNs. One failure mode could be caused by various factors, and the failure location was not necessarily related to the cause of the failure.
This quantitative approach more accurately evaluated the risks of different failure modes, and the results of the corresponding analysis of failure modes and causes could support the rapid determination of the causes of failures in clinical practice.
Ovarian cancer presents a substantial challenge due to its high mortality and recurrence rates among gynecological tumors. Existing clinical chemotherapy treatments are notably limited by drug ...resistance and systemic toxic side effects caused by off target drugs. Sonodynamic therapy (SDT) has emerged as a promising approach in cancer treatment, motivating researchers to explore synergistic combinations with other therapies for enhanced efficacy. In this study, we developed magnetic sonodynamic nanorobot (Fe
O
@SiO
-Ce6, FSC) by applying a SiO
coating onto Fe
O
nanoparticle, followed by coupling with the sonosensitizer Ce6. The magnetic FSC nanorobot collectives could gather at fixed point and actively move to target site regulated by magnetic field.
experiments revealed that the magnetic FSC nanorobot collectives enabled directional navigation to the tumor cell area under guidance. Furthermore, under low-intensity ultrasonic stimulation, FSC nanorobot collectives mediated sonodynamic therapy exhibited remarkable anti-tumor performance. These findings suggest that magnetically actuated sonodynamic nanorobot collectives hold promising potential for application in target cancer therapy.
Ferroptosis is a regulated form of necrotic cell death that involves the accumulation of lipid peroxide (LPO) species in an iron‐ and reactive oxygen species (ROS)‐dependent manner. Previous ...investigations have reported that ferroptosis‐based cancer therapy can overcome the limitations of traditional therapeutics targeting the apoptosis pathway. However, it is still challenging to enhance the antitumor efficacy of ferroptosis due to intrinsic cellular regulation. In this study, a ferroptosis‐inducing agent, i.e., chlorin e6 (Ce6)‐conjugated human serum albumin–iridium oxide (HSA‐Ce6‐IrO2, HCIr) nanoclusters, is developed to achieve sonodynamic therapy (SDT)‐triggered ferroptosis‐like cancer cell death. The sonosensitizing role of both Ce6 and IrO2 within the HCIr nanoclusters exhibits highly efficient 1O2 generation capacity upon ultrasound stimulation, which promotes the accumulation of LPO and subsequently induces ferroptosis. Meanwhile, the HCIr can deplete glutathione (GSH) by accelerating Ir (IV)–Ir (III) transition, which further suppresses the activity of glutathione peroxidase 4 (GPX4) to enhance the ferroptosis efficacy. Through in vitro and in vivo experiments, it is demonstrated that HCIr possesses tremendous capacity to reduce the intracellular GSH content, which enhances SDT‐triggered ferroptosis‐like cancer cell death. Thus, an iridium‐nanoclusters‐based ferroptosis‐inducing agent is developed, providing a promising strategy for inducing ferroptosis‐like cancer cell death.
A bioactive HCIr nanocluster is reported for triggering effective ferroptosis‐like cancer cell death via triggering GPX4 inhibition and concurrent dual sonodynamic effect by iridium oxide nanoclusters and chlorin e6 (Ce6). These HCIr nanoclusters hold a great promise as a ferroptosis‐inducing agent for treating intrinsic apoptotic resistance of tumors, and the findings provide a promising strategy for future studies exploring nanoclusters as anticancer agents.
Fast and effective thrombolysis using tissue plasminogen activator (tPA) is limited by the poor delivery efficiency of thrombolytic drugs, which is induced by an interrupted bloodstream and delayed ...recanalization. Existing magnetic micro/nanodrug‐loaded robots used for targeted thrombotic therapy are limited by the complexity of the clinical verification of nanodrugs and the limited space of magnetic actuation systems. Herein, a general drug delivery strategy based on mass transportation theory for thrombolysis is presented, and an open space C‐shaped magnetic actuation system with laser location and ultrasound imaging navigation for in vivo evaluation is developed. tPA can be guided through an interrupted bloodstream to the thrombi by the locomotion of magnetic nanoparticle swarms (MNSs), thereby improving the thrombolysis efficacy. Notably, this strategy is able to quickly establish a life channel to achieve time‐critical recanalization, which is typically inaccessible using native tPA. Both in vitro and in vivo thrombolysis experiments demonstrate that the thrombus lysis efficacy significantly increases after the application of the MNS under a rotating magnetic field. This study provides an anticipated C‐shaped magnetic actuation system for in vivo validation and also presents a clinically feasible drug delivery strategy for targeted thrombolytic therapy with minimal systemic tPA exposure.
Manipulation of magnetic nanoparticle swarms (MNSs) for thrombolysis is validated in in vivo experiments with an autonomously developed C‐shaped magnetic actuation system. Accompanied by the locomotion of MNSs, a tissue plasminogen activator (tPA) can be transported along with the swarms through the interrupted bloodstream to the clots, thus improving the thrombolysis efficacy and quickly opening a channel for achieving time‐critical recanalization.
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•A concept of “natural product-induced and lactate depletion-enhanced ferroptosis” strategy is proposed for promoting the occurrence of ferroptosis.•The engineered lactic acid ...responsive natural product delivery system presents unique cascade enzymatic/Fenton catalytic performance for distinctive ferroptosis-based anticancer therapy.•The strategy integrating natural product and tumor-specific GPX4 deactivation presents an effective ferroptosis inducing strategy.•This work might provide new insight for realizing effective ferroptosis-based tumor treatment.
Ferroptosis is characterized by the lethal accumulation of lipid reactive oxygen species (ROS), which has great potential for tumor therapy. However, developing new ferroptosis-inducing strategies by combining nanomaterials with small molecule inducers is important. In this study, an enzyme-gated biodegradable natural-product delivery system based on lactate oxidase (LOD)-gated biodegradable iridium (Ir)-doped hollow mesoporous organosilica nanoparticles (HMONs) loaded with honokiol (HNK) (HNK@Ir-HMONs-LOD, HIHL) is designed to enhance ferroptosis in colon tumor therapy. After reaching the tumor microenvironment, the outer LOD dissociates and releases the HNK to induce ferroptosis. Moreover, the released dopant Ir4+ and disulfide-bridged organosilica frameworks deplete intracellular glutathione (GSH), which is followed by GSH-mediated Ir(IV)/Ir(III) conversion. This leads to the repression of glutathione peroxidase 4 (GPX4) activity and decomposition of intratumoral hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) by Ir3+-mediated Fenton-like reactions. Moreover, LOD efficiently depletes lactic acid to facilitate the generation of H2O2 and boost the Fenton reaction, which in turn enhances ROS generation. With the synergistic effects of these cascade reactions and the release of HNK, notable ferroptosis efficacy was observed both in vitro and in vivo. This combination of natural product-induced and lactic acid-responsive sequential production of H2O2 as well as the consumption of glutathione may provide a new paradigm for achieving effective ferroptosis-based cancer therapy.
Magnetic micro‐/nanoparticles are extensively explored over the past decade as active diagnostic/therapeutic agents for minimally invasive medicine. However, sufficient function integration on these ...miniaturized bodies toward practical applications remains challenging. This work proposes a synergistic strategy via integrating particle functionalization and bioinspired swarming, demonstrated by recombinant tissue plasminogen activator modified magnetite nanoparticles (rtPA‐Fe3O4 NPs) for fast thrombolysis in vivo with low drug dosage. The synthesized rtPA‐Fe3O4 NPs exhibit superior magnetic performance, high biocompatibility, and thrombolytic enzyme activity. Benefiting from a customized magnetic operation system designed for animal experiments and preclinical development, these agglomeration‐free NPs can assemble into micro‐/milli‐scale swarms capable of robust maneuver and reconfigurable transformation for on‐demand tasks in complex biofluids. Specifically, the spinning mode of the swarm exerts focused fluid shear stresses while rubbing on the thrombus surface, constituting a mechanical force for clot breakdown. The synergy of the NPs’ inherent enzymatic effect and swarming‐triggered fluid forces enables amplified efficacy of thrombolysis in an in vivo occlusion model of rabbit carotid artery, using lower drug concentration than clinical dosage. Furthermore, swarming‐enhanced ultrasound signals aid in imaging‐guided treatment. Therefore, the pharmacomechanical NP swarms herein represent an injectable thrombolytic tool joining advantages of intravenous drug therapy and robotic intervention.
An injectable thrombolytic tool for fast thrombolysis in vivo using low drug dosage is reported, highlighting synergistic pharmacomechanical function of integrated enzyme‐magnetite (rtPA‐Fe3O4) nanoparticle swarms in rabbit carotid artery.
Insufficient concentrations of intracellular substrates such as hypoxia and H2O2 considerably reduce the effectiveness of reactive oxygen species (ROS)-associated cancer therapy. Modulating the tumor ...microenvironment (TME) for augmenting efficacy has become a promising strategy. Herein, a phase-change cascaded nanomedicine (Lap-IrOx@PCM) was constructed via co-encapsulation of iridium oxide nanozyme (IrOx) and β-lapachone (Lap) by using thermal-responsive phase-change materials (PCMs). After photothermal activation, the protective PCM layer was melted, causing the rapid release of IrOx and Lap. Simultaneously, the peroxidase-like nanozyme IrOx reacted with endogenous H2O2 to liberate highly toxic hydroxyl radicals (•OH) for inducing tumor cell death. Meanwhile, IrOx as another glutathione peroxidase nanozyme also consumed glutathione (GSH) to protect ROS from scavenging. Importantly, the released Lap efficiently generated H2O2 for facilitating the catalytic efficacy of IrOx and provoke the cleavage of heat shock protein 90 (Hsp90) for overcoming tumor heat tolerance in photothermal therapy (PTT). As systematically demonstrated both in vitro and in vivo, this well-defined system achieved a superior antitumor effect via mild photothermal-enhanced nanocatalytic therapy. Our findings have provided the proof of concept of the phase change-mediated, in vivo catalytic activity of nanozymes that can be customized for intensive, TME-mediated, self-enhanced nanocatalytic cancer therapy.
We report a domino-like nanomedicine (Lap-IrOx@PCM) that possesses both H2O2 self-supply and GSH-elimination properties for achieving highly cascaded catalytic-therapeutic outcomes by integrating a peroxidase-like moiety of the IrOx nanozyme and β-Lapachone within a thermal-responsive phase-change material (PCM). This work presents a universal idea of a phase-change nanomedicine design for intensive, mild PTT-enhanced nanocatalytic therapy. Display omitted
•A concept of “phase change nanomedicine-mediated H2O2 self-supplying” strategy is proposed.•β-Lapachone is exploited as a H2O2 productor and heat shock protein inhibitor to fabricate cascade nanocatalyst.•The engineered Lap-IrOx@PCM presents an idea of a phase-change nanomedicine design for intensive nanocatalytic therapy.•This work provides the first example of a nanozyme-type phase-change nanomedicine.
•Electromagnetically actuated magneto-nanozyme synergetic therapy was proposed.•Fe0.73O nanoparticles produces •OH, 1O2, and •O2– in the presence of H2O2.•Magnetic hyperthermia promotes the ...production of •OH, 1O2, and •O2–.•Fe0.73O nanoparticles remove biofilms through physical and chemical effects.
The emergence of bacterial resistance and rapid reconstruction of biofilm pose great challenges to biofilm-associated infections. Magnetically actuated micro-/nanorobots have shown great prospects in various medical applications. In this work, an electromagnetically actuated magneto-nanozyme mediated synergistic therapy (EMST) was proposed and proved to have powerful potential to eradicate biofilm. The developed mesoporous iron oxide nanoparticles (MNPs) with polyvalent iron (0, +2, and +3) simultaneously produce three kinds of reactive oxygen species (ROS, including hydroxyl radical, singlet oxygen, and superoxide anion) in the presence of H2O2, for catalytic bactericidal and degradation of extracellular polymeric substance (EPS) of biofilm. Driven by electromagnetic actuation system, the MNPs were assembled into microswarm to generate shear force and physically destroy biofilm like “sweeping robot”. In addition, the MNP microswarm generates magnetic hyperthermia under alternating magnetic field to promotes the production of ROS, which further improves the bactericidal effect. The excellent anti-infection effects of this EMST were also confirmed in mouse model of skin infection. Overall, this study provides an effective method for the elimination of biofilm infection by combining physical and chemical bactericidal effects.
To overcome the toxicity of chemotherapy, increasing attention has been paid to local drug delivery systems (DDSs). pH-Sensitive hydrogels have emerged as promising DDS materials in the biomedical ...field due to their remarkable characteristics. However, the pH environment in tumor varies from person to person, which makes the applicability of systems based on pH challenging. In this study, we developed a contractible hydroxypropyl methyl cellulose (HPMC)/Fe
O
hydrogel with dual-response pH and magnetic properties aiming to overcome the limitations of pH-sensitive hydrogel drug delivery systems and further increase their efficiency in tumor therapy. The HPMC/Fe
O
hydrogel could act as a drug delivery system that combines pH-sensitive triggering and magnetic dual-response drug release for synergistic chemo-magnetic hyperthermia therapy. The drug delivery profile of the HPMC/Fe
O
/doxorubicin hydrochloride (DOX) hydrogel was determined
and revealed a remarkable pH-sensitive performance. After synergistic chemo-magnetic hyperthermia treatment, mice with 4T1 breast cancer xenografts recovered without any recurrence or metastasis, demonstrating the synergistic effect of chemotherapy and magnetic hyperthermia therapy. Meanwhile, reduced toxicity and superior anticancer effects were achieved due to the combined effect of the pH and magnetic hyperthermia response properties. This study demonstrated the high efficacy and low toxicity of the improved design of HPMC/Fe
O
for drug delivery, which may provide a promising approach for the application of chemo-magnetic hyperthermia cancer therapy.
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