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Small · 2025 · IF 12.1

A pH/GSH Dual-Responsive Triple Synergistic Bimetallic Nanocatalyst for Enhanced Tumor Chemodynamic Therapy

Lu Zhang,Huan Shen,Tingting Liu,Bin Li,Xi Chen,Hong Wang,Chenyang He,Yang Liu,Gang Cao,Shuo Yu

Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (H 2 O 2 ) in tumors into highly toxic hydroxyl radicals (•OH) through metal ion-mediated catalysis. However, the effectiveness of CDT is hindered by low catalyst efficiency, insufficient intra-tumor H 2 O 2 level, and excessive glutathione (GSH). In this study, a pH/GSH dual responsive bimetallic nanocatalytic system (CuFeMOF@GOx@Mem) is developed by modifying red blood cell membranes onto glucose oxidase (GOx)-loaded Fe-Cu bimetallic MOFs, enhancing the efficacy of CDT through a triple-enhanced way by H 2 O 2 self-supply, catalysts self-cycling, and GSH self-elimination. Upon accumulation in tumor tissues facilitated by the red blood cell membrane, the GOx initiates a reaction with glucose to generate H 2 O 2 and gluconic acid in situ. Subsequently, the reduced pH triggers the release of Fe 3+ and Cu 2+ from CuFeMOF@GOx@Mem, which is immediately turned into Fe 2+ and Cu + by GSH, activating the Fe 2+ -mediated Fenton reaction. More importantly, Cu + can also act as an accelerator of Fe 3+ /Fe 2+ conversion, meanwhile, the generated Cu 2+ can be further reduced to Cu + by GSH. Consequently, sustained accumulation of H 2 O 2 and Fe 2+ as well as sustained elimination of GSH are achieved simultaneously, providing a unique approach for improving the anti-tumor ability of CDT.

研究领域: 癌症治疗 · 纳米医学 · 生物化学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Biodegradable Amorphous Copper Iron Tellurite Promoting the Utilization of Fenton-Like Ions for Efficient Synergistic Cancer Theranostics

Huyun Liu,Renting Jiang,Yaxuan Lu,Beibei Shan,Yu Wen,Ming Li

The major hurdles of chemodynamic therapy (CDT) are nondegradability and low-efficiency utilization of chemodynamic agents, and intracellular glutathione (GSH)-induced rapid scavenging of hydroxyl radicals (•OH). Here, a biodegradable a-CFT@IP6@BSA agent is reported for efficient cancer therapy by encapsulating amorphous copper iron tellurite nanoparticles (a-CFT NPs) into inositol hexaphosphate (IP6) and bovine serum albumin (BSA). The biggest merits of this agent are the GSH responsive degradation and amorphous structure, allowing the tumor-specific release of plenty of Cu+ ions and their high-efficiency utilization for •OH production via the Fenton-like reaction. Besides, the released Cu+ ions can deplete the intracellular GSH and thereby protect •OH from scavenging, greatly improving the CDT efficiency. Further, it is found that the a-CFT@IP6@BSA NP treatment down-regulates the levels of glutathione peroxidase 4 and BCL-2, indicating GSH depletion-associated ferroptosis and IP6-induced apoptotic death of cancer cells. Utilizing the T1/T2 dual-modal magnetic resonance imaging capability, the a-CFT@IP6@BSA NPs are demonstrated with excellent in vivo anticancer efficiency and have great potential for imaging-guided cancer treatment.

研究领域: 癌症治疗 · 纳米医学 · 生物医学工程 · 材料科学 · 放射学
✓ 已验证 DOI PubMed 高影响因子
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Small · 2021 ·Vol. 18 ·期 9 ·2105465 · IF 13.281

An Ultrasmall Fe3O4-Decorated Polydopamine Hybrid Nanozyme Enables Continuous Conversion of Oxygen into Toxic Hydroxyl Radical via GSH-Depleted Cascade Redox Reactions for Intensive Wound Disinfection

Jiayu Xiao,Luo Hai,Yaoyao Li,Huan Li,Minhui Gong,Zefeng Wang,Zifeng Tang,Le Deng,Dinggeng He

Nanozyme-based chemodynamic therapy (CDT) for fighting bacterial infections faces several major obstacles including low hydrogen peroxide (H 2 O 2 ) level, over-expressed glutathione (GSH) in infected sites, and inevitable damage to healthy tissue with abundant nonlocalized nanozymes. Herein, a smart ultrasmall Fe 3 O 4 -decorated polydopamine (PDA/Fe 3 O 4 ) hybrid nanozyme is demonstrated that continuously converts oxygen into highly toxic hydroxyl radical (•OH) via GSH-depleted cascade redox reactions for CDT-mediated bacterial elimination and intensive wound disinfection. In this system, photonic hyperthermia of PDA/Fe 3 O 4 nanozymes can not only directly damage bacteria, but also improve the horseradish peroxidase-like activity of Fe 3 O 4 decorated for CDT. Surprisingly, through photothermal-enhanced cascade catalytic reactions, PDA/Fe 3 O 4 nanozymes can consume endogenous GSH for disrupting cellular redox homeostasis and simultaneously provide abundant H 2 O 2 for improving •OH generation, ultimately enhancing the antibacterial performance of CDT. Such PDA/Fe 3 O 4 can bind with bacterial cells, and reveals excellent antibacterial property against both Staphylococcus aureus and Escherichia coli . Most interestingly, PDA/Fe 3 O 4 nanozymes can be strongly retained in infected sites by an external magnet for localized long-term in vivo CDT and show minimal toxicity to healthy tissues and organs. This work presents an effective strategy to magnetically retain the therapeutic nanozymes in infected sites for highly efficient CDT with good biosafety.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 化学 · 细菌学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2020 · IF 10.652

Implantable composite fibres with Self-supplied H2O2 for localized chemodynamic therapy

Gang Wang,Jiayu Gao,Yike Fu,Zhaohui Ren,Jie Huang,Xiang Li,Gaorong Han

The anticancer efficacy of chemodynamic therapy (CDT) is considerably restrained by the inadequate content of H 2 O 2 within tumor microenvironment (TME), unexpected oxidation of Fenton agents and low targeting efficiency of particulate therapeutic platforms. Herein for the first time, an implantable CDT platform was designed and synthesized by combining Fe 0 nanocrystal embedded mesoporous silica nanoparticles (FeMSN) and PCL-gelatin fibres (PG fibres), denoted as [email protected] fibres. FeMSN was fabricated via in situ reduction of ferrous ions within the mesopores of MSNs, and assembled at the surface of electrospun PG fibres by electrostatic interaction to form a fibrous mesh. The findings reflected that, in an acid condition, FeMSN nanoparticles can liberate from the composite fibres, and be effectively uptaken by 4T1 cancer cells. The FeMSN released may react with oxygen to generate H 2 O 2 in the acidic microenvironment, and subsequently transform H 2 O 2 to intracellular hydroxyl radicals, inducing enhanced cell-killing effect. By implanting the composite fibres locally at the tumor site of mice, promoted anticancer efficacy was observed with comparison of the intratumoral-injected FeMSN nanoparticles. This study suggests that [email protected] composite fibres can serve as a potential localized PDT platform for effective antitumor purposes, which may spark a series of follow-on investigations for localized cancer therapeutic technology.

CAS / MDL: 7782-63-0 75-89-8
研究领域: 癌症治疗 · 材料科学 · 纳米技术 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

TME-responded Full-biodegradable nanocatalyst for mitochondrial calcium Overload-induced hydroxyl radical bursting cancer treatment

Wensheng Xie,Jielin Ye,Zhenhu Guo,Jingsong Lu,Wanling Xu,Xiaohan Gao,Hongye Huang,Renjian Hu,Liucheng Mao,Yen Wei,Lingyun Zhao

Mitochondrial calcium ions (Ca 2+ ) overload, an abnormal accumulation of free Ca 2+ in mitochondrial, has become a potential strategy for effective cancer treatment. Inspired by mitochondrial Ca 2+ overload-induced ROS generation, a tumor microenvironment (TME)-responded full-degradable [email protected] 2 O-TPP NCs are successfully fabricated for effective chemodynamic therapy (CDT) via toxic hydroxyl radical ( ∙ O H ) bursting. The as-synthesized nanocatalysts are stable and safe in normal tissues but will quickly degrade into Ca 2+ and cuprous ions (Cu + ) under the acidic TME. The mitochondrial Ca 2+ overload effectively simulates extra H 2 O 2 generation. Then Cu + catalyzes the produced H 2 O 2 into toxic ∙ O H to kill the tumor cells via Fenton-like reaction. Meanwhile, abundant GSH in tumor cells can further reduce Cu 2+ into Cu + to enhance the CDT effect. Both in vitro and in vivo evaluations demonstrate the efficient anti-tumor effect of [email protected] 2 O-TPP NCs via mitochondrial Ca 2+ overload-induced ∙ O H bursting. We believe that the development of [email protected] 2 O-TPP NCs will be an amazing inspiration for designing safe and green chemodynamic nanocatalysts for highly efficient cancer treatment.

研究领域: 肿瘤学 · 纳米技术 · 化学工程 · 生物医学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2021 · IF 5.268

Synergistic anticancer theragnostic study of a core-shell structured galvanic cell

Bao Jiang,Liping Wang,Gang Wu,Lin Zhou,Shaohua Wei

The chemodynamic therapy (CDT) effect is restricted by the neutral pH environment in the tumor, also, the protein corona formed on the surface of the CDT catalyst reduces its activity. Here, we synthesized a core-shell CDT drug consisting of Fe/Fe 3 C core and mesoporous graphite carbon shell with biotin modification (denoted FeCNB). The shell and core form a galvanic cells in the physiological electrolyte solution to achieve high-efficiency CDT under physiological pH conditions. The mesoporous in the shell effectively separates the protein corona from the Fe/Fe 3 C, avoiding the influence of the protein corona on the catalyst. However, the mesoporous is permeable for the substrate and product of the catalytic reaction . FeCNB also has T2-magnetic resonance imaging (MRI) function and photothermal conversion ability under 808 nm laser irradiation. The tumor heating further improves the CDT effect to achieve a satisfactory synergistic photothermal therapy (PTT)/CDT outcome. In addition, FeCNB degrades in the microenvironment to ensure its excellent biocompatibility. It is the first study of CDT drug design and fabrication based on the mechanism of the galvanic cells.

研究领域: 癌症治疗 · 材料科学 · 生物医学工程 · 纳米医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2022 · IF 10.633

GSH-depleting and H2O2-self-supplying hybrid nanozymes for intensive catalytic antibacterial therapy by photothermal-augmented co-catalysis

Junqin Li,Wenhua Yi,Yuze Luo,Ke Yang,Lidan He,Caiyun Xu,Le Deng,Dinggeng He

Nanozyme-based chemodynamic therapy (CDT) has shown tremendous potential in the treatment of bacterial infections. However, the CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H 2 O 2 ) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS 2 /CuO 2 ) is rationally constructed by simply decorating ultrasmall CuO 2 nanodots onto lamellar MoS 2 platelets of hydrangea-like MoS 2 nanocarrier via a covalent Cu-S bond. The MoS 2 /CuO 2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H 2 O 2 produced by acid-triggered decomposition of the decorated CuO 2 into hydroxyl radical (•OH). Meanwhile, the MoS 2 /CuO 2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu 2+ and Mo 6+ ) for enhanced CDT. More importantly, MoS 2 support can promote the conversion of Cu 2+ to Cu + by a co-catalytic reaction based on the Mo 4+ /Mo 6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS 2 /CuO 2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo . Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. Statement of significance Chemodynamic therapy (CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H 2 O 2 ) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS 2 /CuO 2 ) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H 2 O 2 and consuming GSH. Importantly, MoS 2 support can promote the conversion of Cu 2+ to Cu + by the Mo 4+ /Mo 6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS 2 /CuO 2 shows desirable PTT/CDT dual-mode antibacterial efficacy both in vitro and in vivo . This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 治疗学 · 抗菌研究
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MATERIALS LETTERS · 2023 · IF 3

Cu-hemin multilayer nanosheets with integration of peroxidase and photothermal properties for efficient synergistic sterilization

Zitong Wang,Haotian Wu,Yuan Fang,Hao Yang,Xiaomin Wang

The increasing drug resistance of bacteria due to the inappropriate use of various antibiotics has become an ongoing public health problem around the world. In this work, a novel Cu-hemin nanosheet with multilayer structure was synthesized by a simple green method. Integrating the peroxidase properties of hemin with the excellent photothermal conversion performance of IR780, the as-prepared Cu-hemin@IR780 can not only effectively catalyze hydrogen peroxide to produce reactive oxygen species (ROS), but also has a highly efficient and stable photothermal effect for sterilization. The antibacterial efficiency against MRSA can reach up to 98.96% by using chemodynamic therapy (CDT) and photothermal therapy (PTT) for synergistic sterilization.

CAS / MDL: 54827-17-7
研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 微生物学
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Advanced Science · 2024 · IF 14.3

Intraparticle Electron Transfer for Long-Lasting Tumor Chemodynamic Therapy

Jing Yu,Hongmeng Yan,Fan Zhao,Yao Ying,Wangchang Li,Juan Li,Jingwu Zheng,Liang Qiao,Wei Yang,Shenglei Che

Chemodynamic therapy (CDT) is a novel tumor treatment method by using hydroxyl radicals ( • OH) to kill cancer cells. However, its therapeutic effects are strictly confined by the short lifespan of • OH and reduced • OH generation speed. Herein, an effective CDT is achieved by both improving • OH lifetime and long-lasting generating • OH through intraparticle electron transfer within heterogeneous nanoparticles (NPs). These heterogeneous NPs are composed of evenly distributed Cu and Fe 3 O 4 (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to Fe 3 O 4 for the appearance of ≡Cu 2+ and increase in ≡Fe 2+ . The generated ≡Cu 2+ can interact with GSH, which prolongs the lifespan of • OH, produces ≡Cu + for higher speed • OH generation with H 2 O 2 , and induces cell ferroptosis for tumor therapy. The improved ≡Fe 2+ can also improve the • OH release under H 2 O 2 until Cu is depleted. As a result, a sustainable • OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since H 2 O 2 and GSH are only overexpressed at tumor, and CFO NPs can degrade in the tumor microenvironment, these NPs are with high biosafety and can be metabolized by urine. This work provides a novel biomaterial for effective cancer CDT through intraparticle electron transfer.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2022 · IF 9.965

Intelligent Bi2Se3@Cu2−xSe heterostructures with enhanced photoabsorption and photoconversion efficiency for tri-modal imaging guided combinatorial cancer therapy by near-infrared Ⅱ light

Xu Chen,Mengjun Qiu,LiPing Liu,Qin Ji,Zushun Xu,Zhifan Xiong,Shengli Yang

A novel nanoplatform that supports multimodal imaging has been designed for deep tumor therapy. In this study, Bi 2 Se 3 @Cu 2−x Se heterojunction nanocomposites with tunable spectral absorption, effective electron–hole separation and high photothermal conversion efficiency were prepared for the combination therapy of phototherapy (PT), chemodynamic therapy (CDT) and radiotherapy (RT). By adjusting the doping ratio, the heterojunction nanoparticles show obvious tunable ability of local surface plasmon resonance and the ability to promote electron-hole separation with significantly enhanced reactive oxygen species production capacity. The band structure and charge density difference calculated by density functional theory further reveal that the change of band gap and the decrease of free carriers can regulate the spectral absorption of nanomaterials and promote electron-hole separation. In addition, the photothermal conversion properties of low carrier density semiconductors are related to their inherent deep level defects. The formation of heterojunctions making the Se atoms deviate from the Bi 2 Se 3 lattice, resulting in more deep level defects and stronger photothermal conversion properties. Meanwhile, this nanoplatform presented features similar to catalase activities and glutathione (GSH) consumption characteristics, which was capable of effectively alleviate the tumor-specific hypoxia environment to enhance the efficacy of O 2 -dependent photodynamic therapy (PDT) and radiotherapy (RT) and depletion GSH to prevent the reduction of therapeutic efficacy due to the clearance of reactive oxygen species. In addition to therapeutic enhancement, heterojunction nanomaterials have excellent nuclear magnetic resonance imaging (MRI), infrared thermal imaging (IR) and computed tomography (CT) properties due to their significant paramagnetism and excellent photothermal conversion and X-ray attenuation capacities. In conclusion, our findings provide a new strategy for designing multi-function and efficient nanoplatform to treat tumor.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 医学影像
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Intelligent Nanoplatform with Multi Therapeutic Modalities for Synergistic Cancer Therapy

Linjie Shao,Taishun Hu,Xingyu Fan,Xiaozan Wu,Fangfang Zhou,Botao Chen,Songwen Tan,Hui Xu,Anqiang Pan,Shuquan Liang,Yongju He

Chemodynamic therapy (CDT) has attracted increasing attention in tumor treatment but is limited by insufficient endogenous H2O2. Moreover, it is challenging for monotherapy to achieve a satisfactory outcome due to tumor complexity. Herein, we developed an intelligent nanoplatform that could respond to a tumor microenvironment to induce efficient CDT without complete dependence on H2O2 and concomitantly generate chemotherapy and oncosis therapy (OT). The nanoplatform was constructed by a calcium- and iron-doped mesoporous silica nanoparticle (CFMSN) loaded with dihydroartemisinin (DHA). After entering into cancer cells, the nanoplatform could directly convert the intracellular H2O2 into toxic •OH due to the Fenton-like activity of CFMSN. Meanwhile, the acidic microenvironment and endogenous chelating molecules triggered Ca2+ and Fe3+ release from the nanoplatform, causing particle collapse with accompanying DHA release for chemotherapy. Simultaneously, the released Ca2+ induced intracellular Ca2+-overloading for OT, which was further enhanced by DHA, while the released Fe3+ was reduced to reactive Fe2+ by intracellular glutathione, guaranteeing efficient Fenton reaction-mediated CDT. Moreover, Fe2+ cleaved the peroxy bonds of DHA to generate C-centered radicals to further amplify CDT. Both in vitro and in vivo results confirmed that the nanoplatform exhibited excellent anticancer efficacy via the synergistic effect of multi therapeutic modalities, which is extremely promising for high-efficient cancer therapy.

CAS / MDL: 4091-99-0 359010-70-1
研究领域: 纳米技术 · 癌症研究 · 治疗学 · 材料科学
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Biomaterials Science · 2021 ·Vol. 9 ·期 20 ·6830-6841 · IF 6.843

Transdermal delivery of multifunctional CaO2@Mn-PDA nanoformulations by microneedles for NIR-induced synergistic therapy against skin melanoma

Liming Ruan,Gao Song,Xueya Zhang,Tianqi Liu,Yanfang Sun,Junlan Zhu,Zhiyong Zeng,Guohua Jiang

The development of multifunctional nanoformulations (NFs) include several features in a single nanosystem for these devices to overcome the disadvantages of inefficiency and undesirable toxicity of traditional therapies and provide new opportunities in the management of tumors. Herein, multifunctional CaO2@Mn-PDA NFs with a core–shell structure, integrating the photothermal conversion properties of Mn-PDA, the chemodynamic properties of doped Mn ions, and relieving hypoxia in the tumor microenvironment (TME) were developed. The as-fabricated CaO2@Mn-PDA NFs were embedded in microneedles (MNs) for transdermal delivery into tumor sites, leading to the generation of a new minimally invasive and synergistic therapeutic strategy against skin melanoma. Under near-infrared (NIR) light irradiation, the CaO2@Mn-PDA NFs exhibited a synergistic therapeutic effect, including photothermal therapy (PTT), chemodynamic therapy (CDT), and modulating hypoxia due to their high photothermal conversion efficiency, boosted intracellular production of reactive oxygen species, excellent chemodynamic reactions, etc. Therefore, the developed MN platform, which can build implanted multifunctional characteristics for on-demand NIR-induced synergistic therapy, have a bright future in tumor suppression.

研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 药学
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