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Applied Physics Reviews · 2021 ·Vol. 8 ·期 1 · IF 19.162

Self-adaptive enzyme-powered micromotors with switchable propulsion mechanism and motion directionality

Feng Youzeng,Yuan Yue,Wan Jieshuo,Yang Chenglin,Hao Xiaomeng,Gao Zhixue,Luo Ming,Guan Jianguo

Switchable chemotaxis is vital for motile microorganisms seeking benefits or to avoid harm. Inspired by nature, and for the first time, we demonstrate an artificial enzyme-powered micromotor that can autonomously regulate the propulsion mechanism, as well as motion directionality, by solely sensing the change of fuel concentration ( C f ) in its surroundings. The as-designed micromotors have a pot-like microstructure with ureases immobilized on the inner surface. With the confined effect of the pot-like microstructure and unique features of the urease catalytic reaction, the molecular products are further reacted into ions, and their propulsion mechanism can be reversibly adjusted between ionic diffusiophoresis and microbubble recoils when C f changes. Consequently, the as-developed micromotors under magnetic field are able to self-turn back if the local C f differs greatly in their surroundings, indicating the achievement of positive and negative chemotaxis by sensing local C f . Meanwhile, the micromotors also show highly enhanced migration speed by microbubble ejection, up to 60 μm/s, around 30 body lengths per second at physiological urea concentrations. Furthermore, they have an outer surface of mesoporous silica which is easily functionalized for applications such as stimuli-responsive delivery-associated therapies. This work will promote “smart” artificial micro/nanomotors for in vivo biomedical applications.

CAS / MDL: 68-12-2 102-71-6
研究领域: 生物医学工程 · 纳米技术
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2025 · IF 5.4

Enzyme-powered janus upconversion nanomotors for deep tumor penetration and photodynamic therapy

Zhexu Wang,Yanfang Cheng,Bowen Liu,Baohua Zhu,Mingjun Xuan

Photodynamic therapy (PDT) utilizes photosensitizers to generate reactive oxygen species (ROS) for tumor treatment. However, its efficacy is often hindered by the limited tissue penetration and inefficient photosensitizer delivery. The development of upconversion nanoparticles (UCNPs) offers a promising solution to these challenges by converting near-infrared (NIR) light into visible emissions, thereby enabling deeper tissue activation. Herein, we present a urease-powered Janus UCNP nanomotor that combines active photosensitizer delivery with NIR-activated PDT. The nanomotors features a UCNP core and a Janus mesoporous silica shell loaded with chlorin e6 (Ce6), which is further activated by UCNP-emitted visible light under 980 nm NIR irradiation. Through urea decomposition catalyzed by urease, these Janus nanomotors gain self-propulsion capabilities, enhancing cellular uptake and facilitating deep tumor tissue penetration. This active motion markedly improves Ce6 delivery efficiency and promotes ROS generation, thereby enhancing the therapeutic efficacy of PDT. The enzyme-powered Janus UCNP nanomotors present a precise and minimally invasive platform for effective and targeted cancer therapy.

研究领域: 生物医学工程 · 纳米医学 · 癌症治疗
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Photothermal-accelerated urease-powered human serum albumin nanomotor for rapid and efficient photothermal and photodynamic cancer combination therapy

Zhicheng Liu,Shupeng Liu,Xiaoyu Zhao,Chenglong Xue,Yu Liu,Qi Shuai

Nanomotors, as a new type of micro-device, show good performance in terms of rapid transportation and deep penetration through their autonomous motion. However, their ability to efficiently break physiological barriers still remains a great challenge. Herein, we first developed a thermal-accelerated urease driven human serum albumin (HSA) nanomotor based on photothermal intervention (PTI) to achieve chemotherapy drugfree-phototherapy. The [email protected] ( [email protected] @ [email protected] ) is composed of a main body of biocompatible HSA, modified by gold nanorods (AuNR) and loaded with functional molecules of folic acid (FA) and indocyanine green (ICG). It promotes its own motion by breaking down urea to produce carbon dioxide and ammonia. In particular, the nanomotor is conveniently operated via near-infrared combined photothermal therapy (PTT)/ photodynamic therapy (PDT) to achieve an accelerated De value from 0.73 μm 2 s −1 to 1.01μm 2 s −1 , and ideal tumor ablation at the same time. In contrast to customary urease-driven nanodrug-stacked engine, this [email protected] has both targeting and imaging-guided capabilities, and finally achieves superior anti-tumor effects without chemotherapy drugs, through a “two-in-one” (motor mobility plus unique phototherapy in chemotherapy-drugfree phototherapy) strategy. This PTI effect with urease-driven nanomotors may offer further possibilities for future clinical applications of nanomedicines by enabling deep penetration and a subsequent chemotherapy-drugfree combination therapy strategy.

CAS / MDL: 16903-35-8
研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 药学科学
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ACS Nano · 2023 · IF 17.1

Ultrasmall Enzyme-Powered Janus Nanomotor Working in Blood Circulation System

Zili Yang,Liangmeng Wang,Zhixue Gao,Xiaomeng Hao,Ming Luo,Zili Yu,Jianguo Guan

Injectable chemically powered nanomotors may revolutionize biomedical technologies, but to date, it is a challenge for them to move autonomously in the blood circulation system and they are too large in size to break through the biological barriers therein. Herein, we report a general scalable colloidal chemistry synthesis approach for the fabrication of ultrasmall urease-powered Janus nanomotors (UPJNMs) that have a size (100–30 nm) meeting the requirement to break through the biological barriers in the blood circulation system and can efficiently move in body fluids with only endogenous urea as fuel. In our protocol, the two hemispheroid surfaces of eccentric Au−polystyrene nanoparticles are stepwise grafted with poly(ethylene glycol) brushes and ureases via selective etching and chemical coupling, respectively, forming the UPJNMs. The UPJNMs have lasting powerful mobility with ionic tolerance and positive chemotaxis, while they are able to be dispersed steadily and self-propelled in real body fluids, as well as demonstrate good biosafety and a long circulation time in the blood circulation system of mice. Thus, the as-prepared UPJNMs are promising as an active theranostics nanosystem for future biomedical applications.

CAS / MDL: 68-12-2
研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 生物物理学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Engineered platelet cell motors for boosted cancer radiosensitization

Wei Liu,Hongmei Nie,He Li,Ya Liu,Maoye Tian,Shuhuai Wang,Yuwei Yang,Wei Long

Design of engineered cells to target and deliver nanodrugs to the hard-to-reach regions has become an exciting research area. However, the limited penetration and retention of cell-based carriers in tumor tissue restricted their therapeutic efficiency. Inspired by the enhanced delivery behavior of mobile micro/nanomotors, herein, urease-powered platelet cell motors (PLT@Au@Urease) capable of active locomotion, tumor targeting, and radiosensitizers delivery were designed for boosting radiosensitization. The engineered platelet cell motors were constructed by in situ synthesis and loading of radiosensitizers gold nanoparticles in platelets, and then conjugation with urease as the engine. Under physiological concentration of urea, thrust around PLT@Au@Urease motors can be generated via the biocatalytic reactions of urease, leading to rapid tumor cell targeting and enhanced cellular uptake of radiosensitizers. Encouragingly, in comparison with engineered PLT without propulsion capability (PLT@Au), the self-propelled PLT@Au@Urease motors could significantly increase intracellular ROS level and exacerbate nuclear DNA damage induced by γ-radiation, resulting in a remarkably high sensitization enhancement rate (1.89) than that of PLT@Au (1.08). In vivo experiments with 4 T1-bearing mice demonstrated that PLT@Au@Urease in combination with radiation therapy possessed good antitumor performance. Such an intelligent cell motor would provide a promising approach to enhance radiosensitization and broaden the applications of cell motor-based delivery systems.

CAS / MDL: 9013-20-1
研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 放射生物学
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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Nanozyme-chitosan-aerogel immobilized enzyme-driven biocatalytic cascade for therapeutic engineering of diabetic wounds

Bowen Shen,Zhaoxu Yan,Yuxian Wang,Liying Zhu,Qianru Zhao,Ling Jiang

A novel strategy that has emerged in recent years involves the use of aerogels for anti-inflammatory treatment, which has been extensively studied for its powerful application prospects in wound healing, diabetic complications, and tissue regeneration. However, the therapeutic efficacy of aerogels alone is compromised due to bacterial infections at the wound site. Therefore, it is necessary to incorporate effective antibacterial systems onto the aerogels to enhance their efficacy against bacterial infections. For instance, the design of cascade reactions targeting specific disease biomarkers for diagnostic and therapeutic purposes holds promise for enhancing treatment efficacy and precision. In this study, we successfully achieved the immobilization of glucose oxidase within an aerogel prepared from nanozymes, demonstrating remarkable catalytic activity and high-temperature stability. The cascade catalytic system comprising nanozymes and glucose oxidase was applied to combat Methicillin-resistant Staphylococcus aureus (MASR) bacterial infections, exhibiting effective biofilm removal capabilities. In therapeutic experiments on ulcerated wounds in diabetic mice, the cascade catalytic system demonstrated outstanding efficacy with excellent biocompatibility. The therapeutic effects were primarily manifested in the rapid clearance of biofilms formed by MASR, achieved by locally depleting glucose in the wound area, thereby promoting the healing process of ulcerated wounds.

CAS / MDL: 107-21-1 127-09-3
研究领域: 生物技术 · 材料科学 · 药学 · 伤口愈合 · 糖尿病治疗
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ACS Nano · 2019 · IF 13.903

Enzyme-Driven Membrane-Targeted Chimeric Peptide for Enhanced Tumor Photodynamic Immunotherapy

Chi Zhang,Fan Gao,Wei Wu,Wen-Xiu Qiu,Lu Zhang,Runqing Li,Ze-Nan Zhuang,Wuyang Yu,Han Cheng,Xian-Zheng Zhang

Here, a protein farnesyltransferase (PFTase)-driven plasma membrane (PM)-targeted chimeric peptide, PpIX-C6-PEG8-KKKKKKSKTKC-OMe (PCPK), was designed for PM-targeted photodynamic therapy (PM-PDT) and enhanced immunotherapy via tumor cell PM damage and fast release of damage-associated molecular patterns (DAMPs). The PM targeting ability of PCPK originates from the cellular K-Ras signaling, which occurs exclusively to drive the corresponding proteins to PM by PFTase. With the conjugation of the photosensitizer protoporphyrin IX (PpIX), PCPK could generate cytotoxic reactive oxygen species to deactivate membrane-associated proteins, initiate lipid peroxidation, and destroy PM with an extremely low concentration (1 μM) under light irradiation. The specific PM damage further induced the fast release of DAMPs (high-mobility group box 1 and ATP), resulting in antitumor immune responses stronger than those of conventional cytoplasm-localized PDT. This immune-stimulating PM-PDT strategy also exhibited the inhibition effect for distant metastatic tumors when combined with programmed cell death receptor 1 blockade therapy.

CAS / MDL: 72-57-1
研究领域: 癌症生物学 · 药学 · 免疫学 · 分子生物学
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CHEMICAL ENGINEERING JOURNAL · 2019 · IF 8.355

Enzyme-powered Janus nanomotors launched from intratumoral depots to address drug delivery barriers

Zhoujiang Chen,Tian Xia,Zhanlin Zhang,Songzhi Xie,Tao Wang,Xiaohong Li

The delivery of nanoparticles encounters a series of biological barriers from systemic clearance, tumor accumulation, cellular uptake and intracellular drug release. In this study we propose enzyme-powered nanomotors launched from intratumorally injected local depots to overcome these delivery barriers. Hydroxyapatite-embedded mesoporous silica nanoparticles ( [email protected] ) are prepared by formation of silica layers on CaCO 3 nanoparticles, transformation of CaCO 3 into Hap cores, and camptothecin (CPT) loading. Janus nanoparticles (JPs) are obtained by the selective deposition of gold layer on one side of [email protected] Janus nanomotors (JNMs) are constructed by separately grafting hyaluronic acid (HA) and urease on the opposite sides of JPs as the targeting moiety and power source, respectively. JNMs indicate self-propelled motion under the physiological concentration of urea (5 mM), and the motion is less disturbed in the dense tumor matrix. Despite no influence on the endocytosis mechanism, the self-propelled motion and HA-mediated targeting enhance the cellular uptake and cytotoxicity of JNMs. JNMs rapidly release the encapsulated CPT in the acidic endo/lysosomes of tumor cells (pH 5.0) while maintaining their integrity (CTP release <10%) in physiological conditions (pH 7.4) and tumor matrix (pH 6.5). In addition, JNMs are loaded into electrospun fiber fragments ( [email protected] ) for intratumoral administration to achieve a high retention and gradual release of JNMs in response to the slightly acidic tumor matrix (pH 6.5). The self-propelled motion promotes the deep penetration and even distribution of JNMs in tumors, dramatically enhancing the antitumor efficacy. Therefore, the launching of nanomotors from intratumoral depots is a feasible strategy to boost the antitumor efficacy via promoting the local accumulation, deep tumor penetration, tumor cell capture and intracellular release of chemotherapeutic drugs.

研究领域: 纳米技术 · 药学 · 癌症研究 · 生物医学工程
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