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NEW JOURNAL OF CHEMISTRY · 2019 ·Vol. 43 ·期 22 ·8517-8526 · IF 3.069

Preparation of functionalized star polymer nanoparticles by RAFT polymerization and their application in positionally assembled enzymes for cascade reactions

Zhiwu Chen,Hui Cao,Tianwei Tan

A well-defined functional star polymer nanoparticle was prepared using an “arm first” approach via RAFT polymerization. In this work, N-adamantylacrylamide and N-succinimidyl acrylate were copolymerized with N-isopropylacrylamide sucessfully. The obtained diblock copolymer regarded as an “arm” endowed the star polymer with multiple conjugate functions. By adjusting the amount of crosslinking agent, the size and polydispersity of the star polymer were controlled. With the star polymer as the scaffold, a sequential multi-enzyme system was constructed, where HRP was placed in the inner layer through covalent conjugation, and β-cyclodextrin-modified GOx was assembled in the outer layer through host–guest recognition. More interestingly, the activity of the enzyme modified by β-cyclodextrin was improved. In addition to the enhanced thermal stability, this multienzyme system also exhibited a reduced Km value (from 2.18 mM to 0.39 mM) and an excellent substrate affinity. The specificity constant (Kcat/Km) for GOx in the star polymer@HRP@GOx system was 1.7-fold higher than that of the free HRP with free GOx system. This strategy will promote the development of biocatalysis reactions and biosensors as a promising method.

研究领域: 生物化学 · 材料科学 · 生物催化
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MICROCHEMICAL JOURNAL · 2026 · IF 5.2

Integrated smartphone-assisted dual-mode glucose biosensor based on GOx-loaded MOF-derived recyclable Nanozymes for portable diabetes monitoring

Shangyi Zhao,Wenlin Li,Kangjia Liu,Shuang Liu,Mengya Xu,Mengna Wan,Xiaolong Li,Haoxin Gong,Liuqing Cui,Xueqin Wang

The development of portable and highly sensitive sensing platforms is essential for point-of-care diabetes monitoring. The synergistic combination of nanocatalysts with natural enzymes offers a promising strategy for high-performance biomarker detection. Herein, we present a novel dual-mode biosensor for glucose detection that integrates colorimetric and fluorometric readouts into a smartphone-assisted analytical platform. This hybrid design overcomes the inherent instability of natural enzymes and the limited catalytic efficiency of conventional nanozymes through a rationally engineered hybrid nanozyme. The sensing platform was constructed by encapsulating natural glucose oxidase (GOx) within a stable metal-organic framework (MOF) grown on Fe 3 O 4 nanoparticle cores, yielding the composite designated as Fe 3 O 4 @MOF@GOx nanoparticles (FM@GOx NPs). The resulting nanocomposite exhibits enhanced catalytic performance through a synergistic cascade reaction mechanism. The cascade reaction product, oxidized TMB (oxTMB), effectively quenches the fluorescence of Rhodamine B isothiocyanate. Together with the intrinsic color change of oxTMB, this leads to distinct colorimetric and fluorometric shifts, enabling dual-mode detection. The biosensor demonstrates high sensitivity, excellent selectivity, and low detection limits of 0.4 μM (colorimetric) and 2.3 μM (fluorometric). Furthermore, the colorimetric signal is integrated with smartphone-based imaging analysis, wherein captured images are analyzed for their grayscale intensity for real-time glucose quantification. The hybrid nanozyme also shows remarkable stability and can be efficiently recycled multiple times without significant activity loss. The practical applicability was validated by accurately detecting glucose in serum samples from diabetic patients. This integrated and portable sensing platform represents a reliable and user-friendly strategy for diabetes monitoring outside conventional laboratory settings.

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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2025 · IF 5.4

pH-Responsive GOx@Cu-ZIF-8/DOX nanoplatform combines chemodynamic therapy, chemotherapy, and glucose deprivation for enhanced antitumor efficacy

Yaning Li,Yue Wang,Hongchao Ma

The tumor microenvironment (TME), characterized by hypoxia, limited H 2 O 2 availability, and elevated glutathione (GSH) concentrations, challenges reactive oxygen species (ROS)-based therapies. To address these, we developed a GOx@Cu-ZIF-8/DOX (GCZD) nanoplatform combining chemotherapy (CT), chemodynamic therapy (CDT), and starvation therapy (ST). This system utilizes Cu-incorporated ZIF-8 (Cu-ZIF-8) as a versatile carrier to load glucose oxidase (GOx) and doxorubicin (DOX). Under acidic TME conditions, GCZD disintegrates, releasing GOx, Cu 2+ , and DOX. GOx catalyzes intratumoral glucose oxidation, producing gluconic acid and H 2 O 2 to achieve a triple-therapeutic effect. Gluconic acid maintains a weakly acidic environment for continuous GCZD degradation. Glucose depletion induces metabolic starvation. Generated H₂O₂ serves as substrate for Cu 2+ -mediated Fenton-like reactions, boosting ROS production. Cu 2+ exhibits catalytic activity, efficiently converting TME and GOx-generated H 2 O 2 into cytotoxic ·OH. Increased ROS concentration enhances biological macromolecule oxidation damage, intensifying CDT. Additionally, Cu 2+ oxidizes GSH to form GSSH and Cu + . This inhibits GSH-mediated ROS degradation and leverages excellent Fenton-like activity of Cu + to further enhance CDT. Simultaneously, DOX exerts chemotherapeutic effects by intercalating into DNA and inhibiting topoisomerase II, blocking tumor cell proliferation. This integrated approach, combining enhanced ROS generation, tumor cell metabolic intervention, and DNA damage, demonstrates enhanced antitumor efficacy by simultaneously targeting multiple cancer cell vulnerabilities.

CAS / MDL: 10125-13-0 54827-17-7
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Lattice-Like DNA Tetrahedron Nanostructure as Scaffold to Locate GOx and HRP Enzymes for Highly Efficient Enzyme Cascade Reaction

Ding Wang,Yaqin Chai,Yali Yuan,Ruo Yuan

In this work, the array arrangement of cascade enzymes was implemented by alternately and equidistantly anchoring two model enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP) to the vertexes of rigid DNA tetrahedron units in lattice-like nucleic acid scaffold, in which the distance between any adjacent cascade enzymes had been regulated to the optimum for obtaining high enzyme cascade catalytic efficiency. Compared to the enzyme cascade system with no-array arrangement of cascade enzymes, the proposed enzyme cascade system allowed the intermediate H2O2 produced by GOx catalyzing substrate glucose to concurrently and equidistantly diffuse toward the four adjacent HRP enzyme surfaces. In this case, the invalid diffusion effect of intermediate H2O2 between cascade enzymes could be effectively avoided, thereby promoting the enzyme cascade reaction with high catalytic efficiency. The specific catalytic efficiency (kcat/Km) of the cascade enzyme system with array arrangement had been evaluated, which exhibited catalytic efficiency about 3.6 times higher than that of the randomly arranged cascade enzyme system. As a result, this strategy provided a new avenue for constructing a highly efficient enzyme cascade system with ultimate applications in biosynthesis, bioanalysis, and biodiagnostics.

研究领域: 生物化学 · 纳米生物学 · 酶工程
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MICROCHIMICA ACTA · 2023 ·Vol. 190 ·期 3 ·1-10 · IF 5.7

In situ generated PANI promoted flexible photoelectrochemical biosensor for ochratoxin A based on GOx-stuffed DNA hydrogel as enhancer

Tang Juan,Liu Liping,Wang Haiyang,Cheng HongLi,Qin Jiao,Zeng Zhiyao,Lin Youxiu,Tang Dianping,Pu Shouzhi

A flexible photoelectrochemical (PEC) biosensor is proposed for the sensitive detection of ochratoxin A (OTA) based on glucose oxidase (GOx)-encapsulated target-responsive hydrogel, using Fenton reaction-mediated in situ formation of polyaniline (PANI) as signal amplified strategy. The target-responsive DNA hydrogels with high loading capacity can carry a large amount of GOx, which not only avoids laborious labeling process but also enhances the analytical performance. Upon introduction of target molecules, the hydrogel can be opened, and multiple GOx was released, thus producing lots of H 2 O 2 via catalytic reduction of glucose. As a component of the Fenton reagent, H 2 O 2 can react with the Fe 2+ on the graphene oxidase-PAMAM-Fe 2+ (GO-PAMAM-Fe 2+ ) to generate Fe 3+ and ·OH. This in turn can oxidize aniline and generate polyaniline (PANI), resulting in the enhancement of the photocurrent signal of GO-MoS 2 -CdS photoelectrode. The GO-PAMAM-Fe 2+ as the neighborhood component of GO-MoS 2 -CdS-based photoactive material not only can increase the loading amount of Fe 2+ , but also can inhibit the decrease of photocurrent of GO-MoS 2 -CdS by direct modification of Fe 2+ on the photoactive material. Moreover, the high loading capacity of DNA hydrogel can efficiently promote the performance of the PEC biosensor. The PEC biosensor exhibited satisfactory analytical performance for OTA with a linear range of 0.0001–0.1 ng/mL and a low detection limit of 0.05 pg/mL. It presents recommendable specificity, stability, and practical applications. Importantly, the PEC biosensor provides a new concept for construction of PEC biosensing platform. Graphical abstract

研究领域: 食品科学 · 生物传感 · 分析化学
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Advanced Healthcare Materials · 2025 · IF 9.6

Glucose-Responsive Zn(II)-Porphyrin COF Adhesive Hydrogels With Dual-Active Sites and GOX-Like Activity for Accelerated Wound Healing

Jin Wu,Tao Meng,Xiaoqian Zhang,Songtao Tang,Lei Liu,Jing Xue,Xiaohui Liu,Junjun Wang,Jiyue Wen,Danyou Hu,Guiyang Zhang

Effective glycemic control is paramount for optimal wound healing in diabetic patients. Traditional antibacterial and anti-inflammatory treatments, while important, often fall short in addressing the hyperglycemic conditions of diabetic wounds. Therefore, the development of novel therapeutic strategies for accelerating diabetic wound healing has garnered escalating attention. Covalent organic frameworks (COFs) are an emerging class of crystalline porous polymers constructed through strong covalent bonds. Their exceptional structural tunability renders them as an ideal platform for advanced therapeutic applications. Herein, two redox-responsive Zn(II)-coordinated porphyrin COF hydrogels are constructed, which demonstrate rapid blood glucose reduction in localized tissues, along with improved angiogenesis, reactive oxygen species (ROS) scavenging, and photothermal antimicrobial capacities within the hyperglycemic blood environment of diabetic patients, thereby effectively controlling infections and concurrently promoting wound healing. Specifically, COFs with built-in dual active sites, i.e., disulfide or diselenide moieties, can be cleaved by ROS, releasing Zn(II) ions that possess antibacterial and tissue-repairing properties. Furthermore, the Zn(II)-porphyrin COF exhibits glucose oxidase (GOX)-like activity, catalyzing the conversion of glucose into non-glucose metabolites. This synergistic combination of glucose-responsive Zn(II) release and GOX-like activities effectively restores tissue redox balance and improves the wound microenvironment, offering a promising strategy for the diagnosis and treatment of diabetic wounds.

研究领域: 生物材料学 · 医学 · 药理学
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Transboundary and Emerging Diseases · 2026 ·Vol. 2026 ·期 1 ·3527187 · IF 2.6

A Natural Enzyme GOx-MOF Cascade Complex Killing Zoonotic Parasite Trichinella spiralis by Energy Utilization Limitation and Generated Free Radicals

Chuang Zhang,Xiaolei Liu,Zipei Zhang,Zhili Hao,Xu Geng,Ning Jiang,Mingyuan Liu,Zhengqiang Li,Chen Li

Nanozymes offer promising alternatives to natural enzymes due to enhanced stability, tunable activity, and cost efficiency, demonstrating therapeutic potential against tumors, infections, and inflammatory disorders. Trichinella spiralis is an important pathogen, which globally prevalent foodborne zoonotic parasite. Chemical drug is commonly used to kill T. spiralis , but there are risks of chemical abuse and drug resistance. Here, we engineered MPG(Fe), a cascade nanozyme formed by covalently conjugating glucose oxidase (GOx) to a metal-organic framework-Fe nanozyme (MOF-525[Fe]) nanozyme via the bifunctional PEG linker. In vitro, MPG(Fe) depleted glucose through GOx-catalyzed conversion to gluconic acid and H 2 O 2 , while MOF-525(Fe) subsequently transformed H 2 O 2 into cytotoxic hydroxyl radicals (•OH). This dual-action mechanism dose-dependently killed intestinal-stage adult worms and newborn larvae (NBL) of T. spiralis . In a BALB/c mouse model of intestinal T. spiralis infection, high-dose MPG(Fe) reduced the survival of intestinal adult worms to 3.53% of the control value through the synergistic actions of glucose deprivation and hydroxyl radical (•OH)-mediated oxidative damage. Critically, MPG(Fe) exhibited no tissue toxicity in uninfected mice. Our findings establish enzyme-mimetic nanozymes as a novel therapeutic platform against zoonotic helminthiases.

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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Dendritic cross-linked MXene@Fe3O4 for co-immobilization of HRP/GOX bienzyme system and its application in 2,4-dichlorophenol degradation

Xiaozhou Li,Bin Wu,Zhen Gao,Wei Zhuang

To address the challenges of quantitative immobilization and unavoidable spatial hindrance of multiple enzymes in traditional multi-enzyme cascade immobilization, we developed a novel bienzyme immobilization system based on a hierarchically structured MXene@LDHs@Fe₃O₄ (MLF) carrier. The MLF composite, with a high theoretical surface area (∼300 m 2 /g), adjustable interlayer spacing (10–50 nm), and strong magnetization (20 emu/g), provides an ideal support for high-capacity enzyme loading. The system was fabricated through the assembly of MXene nanosheets with layered double hydroxides (LDHs) and magnetic Fe₃O₄ nanoparticles, integrating horseradish peroxidase (HRP) on the MLF core, a polydopamine (PDA) interfacial barrier, and surface-immobilized glucose oxidase (GOx) through melamine-genipin mediated dendritic cross-linking. This spatially organized catalytic architecture enables quantitative enzyme loading while minimizing spatial hindrance, thereby enhancing catalytic efficiency. The co-immobilized bienzyme reactor (GOX@PDA@HRP@MLF) achieved loading capacities of 272.46 mg/g for HRP and 414.33 mg/g for GOx, with an activity recovery of 85.3 % during 2,4-dichlorophenol degradation. The immobilized enzymes retained ∼80 % of their initial activity after five operational cycles. Under optimized conditions, the GOX@PDA@HRP@MLF material achieved a degradation rate of 4.6 for 2,4-dichlorophenol in a continuous flow system, representing a ∼21-fold increase in space-time yield compared to random multi-enzyme immobilization on single-layer resin materials. These results demonstrate that the dendritic cross-linking strategy employed in this study can serve as a universal method for multi-enzyme immobilization, with significant potential for industrial applications.

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TALANTA · 2026 · IF 6.7

A wearable sensor integrating a MXene-PLL-GOx-modified electrode and a Janus nanofibrous membrane for electrochemical monitoring of sweat glucose

Qiujin Li,Xiaoxue Zhu,Jianing Ren,Jingran Su,Jixian Gong,Xiuming Liu,Kuzmichev Victor

A cascade catalytic MXene-PLL-GOx/SPCE electrode is developed for non-invasive and sensitive sweat glucose monitoring. • PLL enables efficient GOx immobilization on MXene through charge regulation and covalent crosslinking. • A PU/PVA Janus nanofiber membrane enables directional sweat transport, while MXene-mediated H 2 O 2 conversion enhances glucose sensing. MXene is a two-dimensional transition metal carbide with large specific surface area, good conductivity, and outstanding biocompatibility, which can be integrated with electrochemical devices, significantly enhancing the sensing performance. Herein, we present a wearable electrochemical sensor based on MXene composites modified electrode and Janus nanofibrous membranes for active sweat collection and precise detection of sweat glucose. Poly- l -lysine (PLL) is highly positively charged because of the -NH 3 + groups, which acts as the crosslinker to bond MXene and glucose oxidase (GOx, containing -COO - groups) both negatively charged, forming a functional composite with high catalytic activity for glucose sensing. In this way, GOx was efficiently immobilized on the MXene nanosheets and then deposited on the screen-printed carbon electrode (SPCE). The intermediate H 2 O 2 from enzymatic glucose oxidation was catalytically decomposed by MXene into H 2 O and O 2 . The recycled O 2 further accelerated the enzymatic reaction on the SPCE. PU/PVA Janus nanofibrous membrane was prepared through electrospinning for active and effective sweat collection due to the unidirectional moisture conduction from its hydrophobic/hydrophilic side. The modified SPCE was integrated with the Janus nanofibrous membrane to fabricate a wearable sweat sensor, with the sensitivities of 16.70 μA mM −1  cm −2 for 0∼300 μM glucose levels, with a detection limit of 24.35 μM. The sensor also showed good stability, selectivity, and reproducibility, providing a new strategy for non-invasive sweat glucose monitoring. Download: Download high-res image (270KB) Download: Download full-size image

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Journal of Materials Chemistry B · 2019 ·Vol. 7 ·期 20 ·3291-3302 · IF 5.047

A novel pH-responsive hollow mesoporous silica nanoparticle (HMSN) system encapsulating doxorubicin (DOX) and glucose oxidase (GOX) for potential cancer treatment

Kaiwu Cheng,Yu Zhang,Yaojia Li,Zhiguo Gao,Fanghui Chen,Kai Sun,Peijing An,Chen Sun,Yong Jiang,Baiwang Sun

The multi-therapy modality is based on the combination and synergy of multiple single treatment modalities and materials chemistry. Herein, a novel pH-responsive doxorubicin (DOX) delivery system based on hollow mesoporous silica nanoparticles (HMSNs) was constructed, which was designed to treat cancer via synergistic chemotherapy and starvation therapy. Logically, starvation therapy could improve the therapeutic efficiency by sensitizing the drug molecules and activating the chemotherapy; glucose oxidase (GOX) coupled to the surface of HMAN deprived the cancer cells of glucose for starvation therapy and increased the abnormality of the tumor microenvironment by locally reducing the pH, aggravating hypoxia and promoting the concentration of poisonous H2O2. Increased acidity could accelerate the depolymerization of pH-sensitive polyelectrolyte multilayers (PEM) wrapped on the most external surface, causing the spatial control of DOX release within tumor cells. Detailed physical characterization certified the successful synthesis of DOX/GOX@HMSN-PEM, which was approximately 180 nm in diameter. In vitro experiments demonstrated that GOX could effectively promote drug release, and DOX/GOX@HMSN-PEM possessed high drug loading rate and stability. Excellent cellular uptake performances were revealed by confocal laser scanning microscopy (CLSM). The positively charged nanoparticles could specifically target the cancer cells overexpressing negative charges. In addition, they were found to have an excellent effect on the cytotoxicity and apoptosis. The promoted drug release via combined starvation therapy and drug therapy suggests that this novel type of pH-responsive hollow mesoporous silica nanoparticles may serve as a new drug delivery system for cancer treatment.

研究领域: 纳米技术 · 材料科学 · 肿瘤学 · 药物化学
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Journal of Environmental Chemical Engineering · 2023 · IF 7.7

Co-immobilization of bienzyme HRP/GOx on highly stable hierarchically porous MOF with enhanced catalytic activity and stability: Kinetic and thermodynamic studies

Xia Gao,Huibin Pan,Siyu Tian,Le Su,Zhanlong Hu,Chengfang Qiao,Qian Liu,Chunsheng Zhou

Immobilization of enzymes onto solid carriers usually results in the reduction of enzyme catalytic activity . To solve this tricky problem, we proposed a novel strategy by accurately constructing the micro-mesoporous channel structure of highly stable hierarchically porous metal-organic framework (HP-Zr-MOF) for co-immobilization of horseradish peroxidase (HRP) and glucose oxidase (GOx). Notably, the precise construction and co-regionalization of HP-Zr-MOF with hierarchical structure can efficiently suppress enzyme leaching and significantly improve the catalytic efficiency, enzyme activity and the affinity for substrates of co-immobilized bienzyme reactor (GOx&HRP@HP-Zr-MOF). The K m value for GOx&HRP@HP-Zr-MOF was 0.2050 mM, which was 0.66-fold less than that of free GOx&HRP, while the K a value for GOx&HRP@HP-Zr-MOF was superior to that of free GOx&HRP, manifesting the affinity of GOx&HRP@HP-Zr-MOF for substrates strengthened. Importantly, the GOx&HRP@HP-Zr-MOF exhibited favorable stability and reusability, maintaining 97.4% of the original activity after 1 h incubation at 60 °C and over 90% initial activity after 30 cycles. Moreover, the GOx&HRP@HP-Zr-MOF was applied to the colorimetric detection of glucose, manifesting outstanding detection capability. Finally, the GOx&HRP@HP-Zr-MOF exhibited excellent catalytic efficiency for the degradation of 2,4-dichlorophenol, which indicated that the bio-catalytic material has potential practical application value in wastewater treatment .

研究领域: 生物化学 · 材料科学 · 环境科学
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International Journal of Nanomedicine · 2024 · IF 6.6

Iron-Based Nanoplatforms Achieve Hepatocellular Carcinoma Regression Through a Cascade of Effects

Kunzhao Huang,Xiaoyuan Yi,Huaying Xie,Jianzhang Luo,Qingyu Zeng,Feifei He,Liyan Wang

Purpose Ferroptosis is a regulated form of cell death characterized by iron-dependent accumulation of associated lipid peroxides (LPO), which can induce cell death when a certain level is reached. However, the extremely complex tumor microenvironment (TME) has the characteristics of antioxidant, even if it induces ferroptosis of tumor cells, its killing effect on tumor cells is still very limited. To solve this problem, we constructed a novel nanomaterials (GOx/EC@Fe3O4@CCM). We evaluated the anticancer effect of this nanomaterial in inhibiting tumor growth through comprehensive in vitro and in vivo experiments.Methods We successfully synthesized GOx/EC@Fe3O4 by one-pan synthesis method, then coated the Hepatocellular carcinoma cell membrane on its surface by co-extrusion technology, and finally synthesized the GOx/EC@Fe3O4@CCM nanoplatforms. We characterized the compounds in terms of morphology, particle size, and Zeta potential. In addition, we also studied the anti-tumor effect of GOx/EC@Fe3O4@CCM nanoplatforms from the following aspects, including the performance test of the nanoplatform, the intracellular effect of the nanoplatform, the anti-tumor effect in vitro, the intracellular ROS analysis, the intracellular effect of EC, and the anti-tumor effect in vivo.Results The iron-based carriers in GOx/EC@Fe3O4@CCM nanoplatforms are released and produce ferrous ions (Fe2+) in an acidic environment. Due to the limitation of the endogenous level of hydrogen peroxide (H2O2), we introduced GOx into the TME or tumor cells. Under the catalysis of GOx, glucose reacted rapidly to produce a large amount of H2O2, which then combined with Fe2+ to produce a large number of Hydroxyl radical (·OH). Its toxicity leads to dysfunction of cell membrane and organelles, and then causes cell damage. EC inhibits Nuclear factor erythroid 2-related factor 2 (Nrf2) in cancer cells, which effectively down-regulates downstream gene products, including NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HMOX1). A series of chain reactions reduce the escape effect of oxidative stress (OS) and effectively maintain a high level of intracellular oxidation. Furthermore, it induces sustained and intense ferroptosis in tumor cells. Finally, the use of cancer cell membrane modified nanoplatforms due to the homology of membrane protein components improves the tumor cell targeting of the nanoplatforms, showing significant tumor cell inhibition and killing effect in vivo.Conclusion The results showed that the GOx/EC@Fe3O4@CCM nanoplatforms successfully induced significant ferroptosis of Hepatocellular carcinoma cells through a cascade effect, and finally effectively promoted cancer cell regression.

研究领域: 癌症研究 · 纳米技术 · 生物化学 · 药理学
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