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IEEE SENSORS JOURNAL · 2024 ·Vol. 24 ·期 24 ·40343-40350 · IF 4.3

Enzyme-Triggered Nanozyme In Situ Synthesis for Patulin Colorimetric/Electrochemical Dual-Mode Sensing

Yixin Pan,Xianwen Kan

The sensitive detection of patulin (PAT) is of paramount important for food safety. Here, a novel colorimetric/electrochemical dual-mode sensor was constructed based on an enzyme-triggered nanozyme in situ synthesis strategy for the sensitive and reliable detection of PAT. Iron metal-organic framework (Fe-MOF) was hydrothermal synthesized on an exfoliated graphene paper (EGP) and utilized as the substrate for sensing. Due to the specific recognition between PAT and its aptamer, alkaline phosphatase (ALP) linked DNA chain was replaced. In the presence of ascorbic acid-phosphate (AAP) and K3[Fe(CN)6], Prussian blue nanoparticles (PB NPs) were in situ synthesized based on the ALP-triggered AAP hydrolysis. The produced ascorbic acid (AA) quickly reduced K3[Fe(CN)6] to K4[Fe(CN)6], which subsequently reacted with Fe-MOF on EGP to form PB NPs. The results showed that PB NPs possessed excellent peroxidase-like activity and electrochemical activity, endowing the sensor with good colorimetric and electrochemical dual-mode sensing abilities. In the presence of H2O2, PB NPs catalytically oxidized o-phenylenediamine (OPD) to form the deep yellow-color production with a distinct color change for colorimetric sensing. The electrochemical mode demonstrated high sensitivity with a lower limit of detection (LOD) of $2.6\times 10^{-{12}}$ g/mL compared to that of the colorimetric mode ( $2.2\times 10^{-{10}}$ g/mL). This portable dual-mode sensor based on ALP-triggered nanozyme in situ synthesis not only offers new insights into sensitive and reliable determination of PAT but also provides an effective way based on visual monitoring and sensitive determination to ensure food safety and health.

研究领域: 食品安全 · 生物传感 · 分析化学
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CHEMISTRY AND PHYSICS OF LIPIDS · 2019 · IF 2.536

A liposomal hydrogel with enzyme triggered release for infected wound

Dandan Li,Xueqin An,Yao Mu

A novel liposomal hydrogel with enzyme triggered release of drug as drug carrier was presented for usage of infected wound. The liposomal hydrogel was prepared by an acombined method of thin-film evaporation and supercritical carbon dioxide technique (TE-scCO 2 ) with freeze-drying. In the liposomal hydrogel, curcumin as a model drug was embedded in the bilayer of the liposomes, and the liposomes were encapsulated in the gelatin-chitosan hydrogel. Phospholipase A 2 (PLA 2 ) riched in wound exudate was served tactfully as a trigger to hydrolyze lecithin in liposome and destroy the liposomes to release drug. Hydrolysis of phospholipids in liposomes was monitored by fluorescence assay of the released curcumin, and relationship between the hydrolysis of lecithin and the release of drug was discussed. The microstructure changes of the liposome after treated by PLA 2 were probed by using florescence probeembedded in the liposomes for the first time. Besides, relationship between the microstructure of liposome and hydrolysis of liposome was revealed. This liposomal hydrogel can not only inhibit the degradation of drug in conveying process and enhance the efficiency of drug release to the infected skin, but also the release of drugs can be on demand by PLA 2 biological activity changed with wound exudate in infected tissue.

研究领域: 药剂学 · 生物材料学
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Intracellular Enzyme-Triggered Assembly of Amino Acid-Modified Gold Nanoparticles for Accurate Cancer Therapy with Multimode

Tao Liu,Ronghua Jin,Pingyun Yuan,Yongkang Bai,Bolei Cai,Xin Chen

Multiple amino acid (glutamine and lysine)-modified gold nanoparticles a with pH-switchable zwitterionic surface were fabricated through coordination bonds using ferrous iron (Fe2+) as bridge ions, which are able to spontaneously and selectively assemble in tumor cells for accurate tumor therapy combining enzyme-triggered photothermal therapy and H2O2-dependent catalytic medicine. These gold nanoparticles showed electric neutrality at pH 7.4 (hematological system) to prevent endocytosis of normal cells, which could be positively charged at pH 6.8 (tumor microenvironment) to promote the endocytosis of tumor cells to these nanoparticles, performing great tumor selectivity. After cell uptake, the specific enzyme (transglutaminase) in tumor cells would catalyze the polymerization of glutamine and lysine to cause the intracellular assembly of these gold nanoparticles, resulting in an excellent photothermal property for accurate tumor therapy. Moreover, the Fe2+ ion could decompose excess hydrogen peroxide (H2O2) in tumor cells via the Fenton reaction, resulting in a large amount of hydroxyl radicals (·OH). These radicals would also cause tumor cell damage. This synergetic therapy associating with high tumor selectivity generated an 8-fold in vitro cytotoxicity against tumor cells compared with normal cells under 48 h incubation with 10 min NIR irradiation. Moreover, in vivo data from tumor-bearing nude mice models showed that tumors can be completely inhibited and gradually eliminated after multimode treatment combining catalytic medicine and photothermal therapy for 3 weeks. This system takes advantage of three tumor microenvironment conditions (low pH, enzyme, and H2O2) to trigger the therapeutic actions, which is a promising platform for cancer therapy that achieved prolonged circulation time in the blood system, selective cellular uptake, and accurate tumor therapy in multiple models.

研究领域: 生物医学工程 · 癌症治疗 · 纳米医学
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Biomaterials Science · 2017 ·Vol. 5 ·期 8 ·1558-1566 · IF 4.21

Phosphatase-triggered cell-selective release of a Pt(IV)-backboned prodrug-like polymer for an improved therapeutic index

Shao-Lu Li,Yingqin Hou,Yali Hu,Jin Yu,Wei Wei,Hua Lu

We describe here the synthesis and cell-selective delivery of a cationic Pt(IV)-backboned prodrug-like polymer P(DSP-DAEP). P(DSP-DAEP) features excellent aqueous solubility, unusually high (44.5%) drug loading, can be rapidly reduced to release the active cisplatin, and is more potent than its small molecular Pt(IV) precursor DSP. P(DSP-DAEP) can be formulated with an oppositely charged methoxyl poly(ethylene glycol)-block-poly(L-phosphotyrosine) (mPEG-b-PpY) to afford a polyion micelle (Pt-PIC) by taking advantage of polyelectrolyte coacervation. Preliminary in vitro cellular uptake and cytotoxicity assays indicate that Pt-PIC exhibits receptor (surface alkaline phosphatase)-dependent uptake and cytotoxicity. Overall, our results suggest a new approach to the improved therapeutic index of platinum-based anticancer drugs via cell-selective delivery.

研究领域: 药物化学 · 肿瘤学 · 生物材料学
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JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY · 2022 · IF 6.76

Fabrication of mesoporous silica-covered gold nanostars for chemophototherapy

Jun Hou,Yanbao Zhao,Lei Sun,Xueyan Zou

Gold nanomaterials have attracted great interest in the fight against cancer due to their surface features. In this study, gold nanostar (GNS) cloaked with mesoporous silica ( [email protected] 2 ) carriers were prepared for controlled drug release. The GNS core presents a branched morphology with tip-to-tip diameter of 80–120 nm and core of 40–60 nm. In this system, GNS not only served as photothermal agent but also as Raman signal enhancement matrix. After encapsulating doxorubicin (DOX) within the [email protected] 2 carrier, hyaluronic acid (HA) was coated on the [email protected] 2 surface to seal the loaded-drug of channels. The obtained [email protected] 2 /HA displayed pH/enzyme-triggered drug release and photothermal-chemo therapeutic effect.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 药学
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International Journal of Polymeric Materials and Polymeric Biomaterials · 2015 · IF 3.568

Charge-Conversional Binary Drug Delivery Polymeric Micelles for Combined Chemotherapy of Cervical Cancer

Qingzhi Guo,Dongdong Guan,Baihua Dong,Fangfang Nan,Youzhong Zhang

Candesartan-g-polyethyleneimine-cis-1,2-cyclohexanedicarboxylic anhydride (CD-g-PEI-HHPA, CPH) polymer-drug conjugates based on charge-conversional delivery, enhanced buffering capacity, amidase-triggered drug release, and combined cancer chemotherapy strategies were successfully synthesized for simultaneous and effective codelivery of CD and paclitaxel (PTX) to treat cervical cancer. The CPH polymer-drug conjugates could self-assemble into core-shell structure micelle of around 100 nm in diameter with negative surface charge and were employed to load PTX to formulate binary drug delivery system. The CPH polymeric micelles could mediate quick endosomal escape and amidase-responsive drug-release manners. In vitro cytotoxicity and in vivo investigations confirmed CPH binary drug delivery system exerted strong antitumor efficacy.

研究领域: 药学 · 肿瘤学 · 药物递送系统 · 聚合物化学
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2023 · IF 5.2

Fabrication of badminton-like porous silica carriers and their application in drug release

Jiaqi Lu,Weiting Zhong,Jun Hou,Yanbao Zhao

Current research on silica-based drug delivery systems (DDS) mainly focuses on spherical silica nanocarriers , but asymmetric silica carriers display improving uptake efficiency. In this paper, asymmetric mesoporous silica (AMS) nanocarriers were designed and prepared by asymmetric modification. The AMS sample presents badminton-like structure with head of about 250 nm and tail length of 60–70 nm. Compared with spherical carriers, the AMS carriers displayed higher cell uptake efficiency. When doxorubicin (DOX) was loaded, hyaluronic acid (HA) molecules were used to block the loaded-drug. HA layer was easily degraded by endogenous hyaluronidase (HAase) or acidic environment. The obtained [email protected] displayed pH/enzyme-triggered drug release.

研究领域: 材料科学 · 药学 · 纳米技术
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Pectinase-responsive UiO-66-COOH/pectin coating system for targeted release of potassium cinnamate: A novel strategy for smart fruit preservation

Jinlong Li,Zihuan Zhao,Qihang Wei,Hongman Hou,Gongliang Zhang,Jingran Bi

This study integrates UiO-66-COOH metal–organic frameworks (MOFs) with pectin (Pec) to precisely release potassium cinnamate (PC) to develop a pectinase-responsive active fruit-preservation system (UiO-66-COOH@PC/Pec). Carboxylated UiO-66 with nanoporosity was fabricated to achieve a high loading amount of PC (235 mg·g −1 ) via the synergistic effects of hydrogen bonding, as shown by the loading kinetics and reduced density gradient analyses. A gatekeeper was established by grafting Pec onto the surface of the MOF (UiO-66-COOH@PC/Pec), thereby “locking” PC to prevent leakage. Moreover, an enzyme-responsive controlled-release behavior was developed under pectinase stimulation, achieving up to 95 % PC release within 9 h through Fickian diffusion and only 25.3 % in enzyme-free conditions by non-Fickian diffusion and matrix erosion. With significant long-term inhibiting activity against both bacteria and fungi, UiO-66-COOH@PC/Pec successfully extended the shelf life of strawberries from 2 to 5 days at 25 °C. Moreover, UiO-66-COOH@PC/Pec exhibited good water solubility and negligible toxicity, indicating that it can be easily removed from fruit surfaces and offers high consumer acceptance. These results provide a novel MOF-based controlled-release strategy for smart food-packaging applications.

CAS / MDL: 9000-69-5 9032-75-1
研究领域: 食品科学与技术 · 材料科学 · 智能包装 · 可控释放系统 · 采后生物学与技术
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE · 2018 ·Vol. 29 ·期 11 ·1-12 · IF 2.448

Fabrication of enzyme-responsive composite coating for the design of antibacterial surface

Liu Peng,Hao Yansha,Ding Yao,Yuan Zhang,Liu Yisi,Cai Kaiyong

In this study, a type of bacteria enzyme-triggered antibacterial surface with a controlled release of Ag ions was developed. Firstly, chitosan-silver nanocomposites (Chi@Ag NPs) were in situ synthesized via using ascorbic acid as reducing agent. Chi@Ag NPs were characterized by transmission electron microscopy, ultraviolet–visible spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Subsequently, Chi@Ag NPs and hyaluronic acid (HA) were used to fabricate antibacterial composite coating via Layer-by-Layer (LBL) self-assembly method. The successful construction of Chi@Ag NPs/HA composite coating was confirmed by scanning electron microscopy, energy dispersive spectroscopy and contact angle measurements, respectively. Then, the amount of released Ag ion was analyzed by inductively coupled plasma atomic emission spectrometry, which demonstrated that the release of Ag ions from the surface could be triggered by enzyme (e.g. hyaluronidase). A series of antibacterial tests in vitro, including zone of inhibition test, bacterial viability assay, antibacterial rate measurement and bacteria adhesion observation, demonstrated that the enzyme-responsive surface could inhibit the growth of bacteria. On the whole, this study provides an alternative approach for the fabrication of antibacterial surfaces on synthetic materials in various fields with the minimal side effects on surrounding environment and human body.

CAS / MDL: 9067-32-7
研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 表面化学
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Gels · 2025 ·Vol. 11 ·期 8 ·654 · IF 5.3

Enzyme-Triggered Formation of Tensegrity Structures for Mechanospatial Manipulation of Hydrogels

Juan Wang,Xu Han,Qingtai Li,Meng Qin,Bin Xue,Wenxu Sun,Yi Cao,Wei Sun

Hydrogels with spatially programmable mechanical properties hold great potential for use in biomedical applications. Inspired by the architecture of the cytoskeleton, we present a strategy for constructing tensegrity-structured hydrogels (TS-Gels) through enzyme-triggered crystal growth to enable precise mechanospatial manipulation. Specifically, alkaline phosphatase (ALP) was covalently anchored to a polyacrylamide (PAAm) hydrogel matrix to catalyze the in situ dephosphorylation of phosphotyrosine precursors, leading to the formation of rigid tyrosine crystals. These crystals functioned as compressive sticks, establishing tensegrity structures within the hydrogel network. By tuning the crystallization kinetics, both the structural morphology and mechanical reinforcement could be precisely controlled. The resulting TS-Gels exhibited significantly enhanced local tensile strength and stiffness, allowing for spatial–mechanical patterning via photo-initiated printing, mold-assisted shaping, and laser engraving. Furthermore, the unique mechanospatial tunability of TS-Gels was demonstrated in tribological surface engineering, underscoring their potential for use in tissue engineering and responsive biomaterials.

CAS / MDL: 2530-85-0
研究领域: 生物材料 · 组织工程 · 软物质物理 · 材料科学 · 生物医学工程
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Journal of Materials Chemistry B · 2018 ·Vol. 6 ·期 48 ·8090-8104 · IF 4.776

Surface engineering of titanium implants with enzyme-triggered antibacterial properties and enhanced osseointegration in vivo

Zhang Yuan,Suzhou Huang,Shaoxiong Lan,Haizhou Xiong,Bailong Tao,Yao Ding,Yisi Liu,Peng Liu,Kaiyong Cai

Preventing bacterial infection and improving the osseointegration of titanium (Ti) and its alloys are both highly crucial factors for their long-term successful implantation in clinical applications. However, the straightforward applications of antibacterial surfaces on Ti-based materials remain limited due to their side effects on cytocompatibility. Herein, catechol-functionalized multilayer films composed of dopamine-modified hyaluronic acid (HA-c) and 3,4-dihydroxyhydrocinnamic acid-modified chitosan (Chi-c) were developed on Ti substrates modified with TiO2 nanotube arrays loaded with an antibacterial drug. The treated Ti substrate showed strong hydrophilicity, with a water contact angle of about 20°, and obviously inhibited early-stage bacterial adhesion. Moreover, this system displayed an enzyme-responsive release of antibacterial drug triggered by the hyaluronidase degradation of HA-c, which exhibited effective antibacterial ability and eliminated side effects caused by burst release of antibiotics. Meanwhile, the modified Ti substrates significantly promoted initial osteoblast adhesion through up-regulating the expression of adhesion-related genes, including integrin αv and β3. More importantly, this prepared coating with bacterial self-responsiveness improved osseointegration and prevented bacterial infection of Ti implants in vivo. Overall, our developed catechol-functionalized and bacterial self-responsive coating on Ti substrate has great significance in clinical applications of orthopedic and dental implants.

CAS / MDL: 9067-32-7
研究领域: 生物材料 · 生物医学工程 · 组织工程 · 骨科 · 牙科种植学
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Journal of Materials Chemistry B · 2024 · IF 6.1

Enzyme-triggered on-demand release of a H2O2-self-supplying CuO2@Fe3O4 nanoagent for enhanced chemodyamic antimicrobial therapy and wound healing

Sijie Zhang,Sameer Hussain,Yuhai Tang,Kaili Wang,Xingyan Wang,Long Zhang,Yuheng Liao,Chen Wang,Yi Hao,Ruixia Gao

Nanoagents for chemodynamic therapy (CDT) hold a promising future in the field of antimicrobials, especially copper peroxide (CuO2) (CP) nanomaterials which have garnered significant attention due to their ability to self-supply H2O2. Nevertheless, the poor stability of CuO2 remains a critical challenge which restricts its practical application in the antibacterial field. In this study, an advanced nano-antimicrobial system HA-CP@Fe3O4 with enzyme-responsive properties is developed by coating hyaluronic acid (HA) on CuO2-loaded iron tetraoxide nanoparticles. The coating of HA not only stabilizes the CuO2 nanomaterials but also provides responsiveness towards the enzyme hyaluronidase, which is typically secreted by some bacteria. The outer layer of HA in HA-CP@Fe3O4 undergoes decomposition in the presence of hyaluronidase-secreting bacteria, resulting in the release of CuO2@Fe3O4. The released CuO2@Fe3O4 then self-supplies H2O2 and generates reactive oxygen species (ROS) within the infected microenvironment through Fenton and Russell effects, to ultimately achieve effective and precise antimicrobial activity. Simultaneously, the magnetic property provided by Fe3O4 allows the substance to be directed towards the infection site. Both in vitro and in vivo tests demonstrated that HA-CP@Fe3O4 exhibited excellent antimicrobial capabilities at low concentration (30 μg mL−1), exceptional biocompatibility and the ability to accelerate wound healing. The findings of this work offer a new and promising approach for targeted and precise CDT.

研究领域: 纳米技术 · 生物医学工程 · 抗菌治疗 · 伤口愈合 · 材料科学
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