As the first line of host defense against invading pathogens, neutrophils have an inherent phagocytosis capability for the elimination of foreign agents and target loading upon activation, as well as the ability to transmigrate across blood vessels to the infected tissue, making them natural candidates to execute various medical tasks in vivo. However, most of the existing neutrophil-based strategies rely on their spontaneous chemotactic motion, lacking in effective activation, rapid migration, and high navigation precision. Here, we report an optically manipulated neutrophil microcraft in vivo through the organic integration of endogenous neutrophils and scanning optical tweezers, functioning as a native biological material and wireless remote controller, respectively. The neutrophil microcrafts can be remotely activated by light and then navigated to the target position along a designated route, followed by the fulfillment of its task in vivo, such as active intercellular connection, targeted delivery of nanomedicine, and precise elimination of cell debris, free from the extra construction or modification of the native neutrophils. On the basis of the innate immunologic function of neutrophils and intelligent optical manipulation, the proposed neutrophil microcraft might provide new insight for the construction of native medical microdevices for drug delivery and precise treatment of inflammatory diseases.
Precise building of multifunctional nano/microarchitectures holds exciting prospects in various biomedical applications such as drug delivery, biosensing, and disease diagnosis. However, the reported architectures still face great challenges when implemented in vivo due to insufficient biocompatibility, inevitable invasiveness, low stability, and difficulty for reconfiguration. Here, we report an optically reconfigurable platelet architecture through an organic integration of programmable optical manipulation and intravital platelets, functioning as highly skilled mason and endogenous biological blocks, respectively. By programming the optical force landscape in real time, multiple platelets can be stably trapped and then precisely arranged into a designed pattern, followed by spontaneous binding through the robust interaction between membrane protein and ligands, thus achieving a stable biological architecture with a high navigation flexibility. More importantly, they can be sculptured in a dynamically reconfigurable manner, with the aim to execute multifunctional biomedical tasks, including the active circumventions across the obstacles, precise vessel labeling, blood flow switching, and targeted cargo delivery. The reported platelet architecture might serve as a smart biomedical platform for constructing multifunctional cellular micromachines, with great promises for the desired biomanufacturing, targeted drug delivery, and immune therapy.
Living Red Blood Cell Microrouter In article number 2304103, Xiaoshuai Liu, Xianchuang Zheng, Baojun Li, and co-workers develop a living microrouter based on an organic integration of endogenous red blood cells, programmable scanning optical tweezers, and flexible optofluidic strategy, under which various biological targets could suffer from a selective routing by integrating the three successive functions, i.e., dynamic input, inner processing, and controlled output.
Biosensing In article number 2205760, Xiaoshuai Liu, Xianchuang Zheng, and co-workers introduce an optically controlled virtual microsensor (OCViM) for biomarker detection in vivo. In this new technique, light serves as the virtual handle to manipulate the sensor tip and also excite it to generate fluorescence emission for biosensing. This new technique combines the features of the needle-type microelectrode and the fluorescence imaging method, leading to significant advantages including noninvasiveness, active control, and high resolution.
The miniaturization of biomedical microrobots is crucial for their in vivo applications. However, it is challenging to reduce their size while maintaining their biomedical functions. To resolve this contradiction, we propose a semiphysical design concept for developing miniaturized microrobots, in which invisible components such as light beams are utilized to replace most of the physical parts of a microrobot, thus minimizing its physical size without sacrificing its biomedical functions. According to this design, we have constructed a semiphysical microrobot (SPM) composed of main light beam, light-responsive microparticle, and auxiliary light beam, serving as the actuation system, recognition part, and surgical claws, respectively. Based on the functions of actuation, biosensing, and microsurgery, a SPM has been applied for a series of applications, including thrombus elimination at the branch vessel, stratified removal of multilayer thrombus, and biosensing-guided microsurgery. The proposed semiphysical design concept should bring new insight into the development of miniaturized biomedical microrobots.
Abstract Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB‐DiOH) which can reversibly respond to hypochlorite (ClO−)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real‐time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI.
The active delivery of nanodrugs has been a bottleneck problem in nanomedicine. While modification of nanodrugs with targeting agents can enhance their retention at the lesion location, the transportation of nanodrugs in the circulation system is still a passive process. The navigation of nanodrugs with external forces such as magnetic field has been shown to be effective for active delivery, but the existing techniques are limited to specific materials like magnetic nanoparticles. In this study, an alternative actuation method is proposed based on optical manipulation for remote navigation of nanodrugs in vivo, which is compatible with most of the common drug carriers and exhibits significantly higher manipulation precision. By the programmable scanning of the laser beam, the motion trajectory and velocity of the nanodrugs can be precisely controlled in real time, making it possible for intelligent drug delivery, such as inverse-flow transportation, selective entry into specific vascular branch, and dynamic circumvention across obstacles. In addition, the controlled mass delivery of nanodrugs can be realized through indirect actuation by the microflow field. The developed optical manipulation method provides a new solution for the active delivery of nanodrugs, with promising potential for the treatment of blood diseases such as leukemia and thrombosis.
The delivery of NO at a high spatiotemporal precision is important but still challenging for existing NO-releasing platforms due to the lack of precise motion control and limited biomedical functions. In this work, we propose an alternative strategy for developing the light-armed nitric oxide-releasing micromotor (LaNorM), in which a main light beam was employed to navigate the microparticle and stimulate NO release and an auxiliary light beam was used to cooperate with the released NO to act as a remotely controlled scalpel for cell separation. Benefiting from the advantages of fully controlled locomotion, photostimulated NO release, and microsurgery ability at the single-cell level, the proposed LaNorM could enable a series of biomedical applications
Current technologies for the real-time analysis of biomarkers in vivo, such as needle-type microelectrodes and molecular imaging methods based on exogenous contrast agents, are still facing great challenges in either invasive detection or lack of active control of the imaging probes. In this study, by combining the design concepts of needle-type microelectrodes and the fluorescence imaging method, a new technique is developed for detecting biomarkers in vivo, named as "optically controlled virtual microsensor" (OCViM). OCViM is established by the organic integration of a specially shaped laser beam and fluorescent nanoprobe, which serve as the virtual handle and sensor tip, respectively. The laser beam can trap and manipulate the nanoprobe in a programmable manner, and meanwhile excite it to generate fluorescence emission for biosensing. On this basis, fully active control of the nanoprobe is achieved noninvasively in vivo, and multipoint detection can be realized at sub-micrometer resolution by shifting a nanoprobe among multiple positions. By using OCViM, the overexpression and heterogenous distribution of biomarkers in the thrombus is studied in living zebrafish, which is further utilized for the evaluation of antithrombotic drugs. OCViM may provide a powerful tool for the mechanism study of thrombus progression and the evaluation of antithrombotic drugs.
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