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二氧化锰 (MnO2)
Scientific Reports · 2018 ·Vol. 8 ·期 1 ·1-9 · IF 4.122

MRI/Fluorescence bimodal amplification system for cellular GSH detection and tumor cell imaging based on manganese dioxide nanosheet

Yuan Dandan,Ding Lairong,Sun Zhaomei,Li Xuemei

Here, we report a novel magnetic resonance imaging (MRI)/fluorescence bimodal amplification platform for the detection of glutathione (GSH) on the basis of redoxable manganese dioxide (MnO 2 ) nanosheets, which can be readily applied as a DNA nanocarrier, fluorescence quencher, and intracellular GSH-activated MRI contrast agent. The binding of aptamers that absorbed on the MnO 2 nanosheets to their target can facilitating the endocytosis of target-nanoprobes. Once endocytosed, the MnO 2 nanosheets can react with cellular GSH, resulting in the disintegration of nanosheets to generate plenty of Mn 2+ ions for MRI and releases the primers which were adsorbed on the MnO 2 nanosheets. Then the rolling circle amplification (RCA) reaction was initiated to amplify the fluorescence signal. In addition, after treatment with GSH, the MnO 2 nanosheets were reduced and then most of the fluorescence was recovered. Therefore, this MnO 2 nanoprobe exhibits excellent selectivity, suggesting a potential detection platform for analyzing the glutathione level in cells.

CAS / MDL: 13446-34-9
研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 分子成像
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 17 ·3677-3688 · IF 6.331

MnO2-capped silk fibroin (SF) nanoparticles with chlorin e6 (Ce6) encapsulation for augmented photo-driven therapy by modulating the tumor microenvironment

Lei Zhang,Ruihao Yang,Honglian Yu,Zhigang Xu,Yuejun Kang,Hongjuan Cui,Peng Xue

Silk fibroin (SF), derived from Bombyx mori, is a category of fibrous protein with outstanding potential for applications in the biomedical and biotechnological fields. In spite of its many advantageous properties, the exploration of SF as a versatile nanodrug precursor for tumor therapy has still been restricted in recent years. Herein, a multifunctional SF-derived nanoplatform was facilely developed via encapsulating the photosensitizer chlorin e6 (Ce6) into MnO2-capped SF nanoparticles (NPs). SF@MnO2 nanocarriers were synthesized through a surface crystallization technique, using SF as a reductant and sacrificial template. Afterwards, Ce6 was covalently incorporated into the loose structure of the SF@MnO2 nanocarrier on the basis of adsorption to abundant peptide-binding sites. To modulate the tumor microenvironment (TME), SF@MnO2/Ce6 (SMC) NPs were capable of catalyzing the decomposition of H2O2 into O2, which can be converted into cytotoxic reactive oxygen species (ROS) during photodynamic therapy (PDT). Moreover, the MnO2 component was able to oxidize intracellular glutathione (GSH) into non-reducing glutathione disulfide (GSSG), and the consumption of GSH could significantly protect the local ROS from being reduced, which further augmented the therapeutic outcome of PDT. Via another angle, SMC NPs can produce strong hyperthermia under near-infrared (NIR) light activation, which was highly desirable for efficient photothermal therapy (PTT). Both in vitro and in vivo studies demonstrated the intense tumor inhibitory effects as a result of augmented PTT/PDT mediated by SMC NPs. We believe that this study may provide useful insights for employing SF-based nanocomposites for more medical applications in the near future.

研究领域: 生物医学工程 · 纳米医学 · 癌症治疗 · 材料科学
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LUMINESCENCE · 2017 ·Vol. 33 ·期 1 ·138-144 · IF 1.509

Redox luminescence switch based on Mn2+-doped NaYF4:Yb,Er upconversion nanorods

Liping Zhang,Jianguo Zhang,Hongqi Chen,Lun Wang

An redox luminescence switch was developed for the sensing of glutathione (GSH), l -cysteine (Cys) or l -ascorbic acid (AA) based on redox reaction. The Mn 2+ -doped NaYF 4 :Yb,Er upconversion nanorods (UCNRs) with an emission peak located in the red region were synthesized. The luminescence intensity of the UCNRs could be quenched due to the Mn 2+ could be oxidized to MnO 2 by KMnO 4 . Subsequently, when the AA, GSH or Cys was added into the MnO 2 modified upconversion nanosystem, which could reduced MnO 2 to Mn 2+ and the luminescence intensity was recovered. The concentration ranges of the nanosystem are 0.500–3.375 mM (R 2 = 0.99) for AA, 0.6250–11.88 mM (R 2 = 0.99) for GSH and 0.6250–9.375 mM (R 2 = 0.99) for Cys, respectively.

研究领域: 分析化学 · 纳米技术 · 生物化学
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 26 ·5255-5263 · IF 6.331

Oxygen-producing proenzyme hydrogels for photodynamic-mediated metastasis-inhibiting combinational therapy

Jiansheng Liu,Xueqin Qing,Qin Zhang,Ningyue Yu,Mengbin Ding,Zhaohui Li,Zhen Zhao,Zhiling Zhou,Jingchao Li

Photodynamic therapy (PDT) has provided a promising approach for the treatment of solid tumors, while the therapeutic efficacy is often limited due to the hypoxic tumor microenvironment, resulting in tumor metastasis. Herein, we report an oxygen-producing proenzyme hydrogel (OPeH) with photoactivatable enzymatic activity for PDT enabled metastasis-inhibiting combinational therapy of breast cancer. This OPeH based on alginate is composed of protoporphyrin IX (PpIX) conjugated manganese oxide (MnO2) nanoparticles, which act as both the photosensitizer and oxygen-producing agent, and singlet oxygen (1O2)-responsive proenzyme nanoparticles. In the hypoxic and acidic tumor microenvironment, MnO2 can generate 1O2 to promote PpIX-mediated PDT with an amplified 1O2 generation efficiency, which also triggers the cleavage of 1O2-responsive linkers and cascade activation of proenzymes for cancer cell death. This combinational therapy upon photoactivation not only greatly inhibited the tumor growth, but also suppressed lung metastasis in a mouse xenograft breast tumor model, which is impossible in the case of PDT alone. This study thus provides a proenzyme hydrogel platform with photoactivatable activity for metastasis-inhibiting cancer therapy with high efficacy and safety.

研究领域: 癌症治疗 · 纳米医学 · 生物医学工程 · 肿瘤微环境研究
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ACS Applied Nano Materials · 2023 · IF 5.9

NaErF4-Based Nanocarrier for Enhanced Ferroptosis Therapy of Cancer

Jin-Yang Liu,Na Liu,Yue Wu,Xiao-Min Ning,Wen-Chao Zhang,Jing Qian

To improve the treatment efficiency of ferroptosis and accurately monitor the therapy process, we developed small-sized upconversion nanoparticles (UCNPs) by a simple one-step solvothermal method. On this basis, a facile strategy is reported to construct mesoporous SiO2-coated UCNPs as the nanocarrier to load dual drugs of MnO2 and methylene blue (MB) photosensitizer for hypoxic tumor theranostic. Due to the components of high charge elements, the synthetic NaErF4:Yb,Gd,Eu@mSiO2/MnO2/MB@FA (UPSMF/MB, FA = folic acid) exhibited radiosensitization function. Emitting strong red upconversion luminescence (UCL) excited the encapsulated MB to initiate photodynamic therapy (PDT). In addition, UPSMF/MB released green UCL imaging in vivo, so as to trace drug distribution and achieve accurate theranostic. In tumor microenvironment, the loaded MnO2 possessed catalase-like (CAT) catalytic activity, which could effectively decompose excessive H2O2 into O2, thus alleviating hypoxia in the tumor area and promoting PDT and radiotherapy (RT) to generate reactive oxygen species (ROS). Furthermore, MnO2 had excellent glutathione peroxidase (GPx)-like activity, which could effectively decompose intracellular over-expressed glutathione (GSH), thus causing lipid peroxide (LPO) accumulation and inducing ferroptosis. In situ ROS generation by PDT and RT further promoted the accumulation of intracellular LPO. Cytotoxicity assay revealed that the apoptosis rate of UPSMF/MB promoted by RT and PDT was 79.76%, which was 46% higher than that of solo ferroptosis induced by UPSMF. Notably, in vivo results illustrated that the tumor inhibition rate of UPSMF/MB could be increased to 83.4% under the triple effects of RT, PDT, and ferroptosis with negligible side effects to normal tissues. This work paves a way to enhance the efficacy of ferroptosis-based cancer therapy by associating PDT with RT.

研究领域: 癌症研究 · 纳米技术 · 诊疗一体化 · 生物医学工程 · 材料科学
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International Journal of Nanomedicine · 2022 · IF 7.033

GOx-Functionalized Platelet Membranes-Camouflaging Nanoreactors for Enhanced Multimodal Tumor Treatment

Ying Du,Shujun Wang,Jianfeng Luan,Meilin Zhang,Baoan Chen,Yanfei Shen

Background Glucose oxidase (GOx)-based starvation therapy is a new cancer treatment strategy. However, the characteristics such as limited curative effect and hypoxic tumor environment hinder its further application seriously.Methods Herein, doxorubicin (DOX) loaded in hollow mesoporous copper sulfide (HMCuS) nanoparticles assembled with manganese dioxide (HMMD) as nanoshell was prepared. We developed a targeted enhanced cancer treatment method to camouflage HMMD by GOx-functionalized platelet (PLT) membranes (HMMD@PG).Results GOx can be specially transported to the tumor site with PLT membrane for effective starvation treatment. Glucose and oxygen (O2) in the tumor were converted to H2O2 under the catalysis of GOx. HMMD can catalyze H2O2 to produce O2 and consume glutathione (GSH) in time, which regulates the tumor microenvironment (TME) and improves the adverse conditions of anti-tumor. In addition, DOX encapsulated in HMCuS-MnO2 release was accelerated from the nanoparticles after the “gatekeeper” MnO2 is consumed. The study of anti-tumor mechanism shows that the remarkable tumor suppressive ability of HMMD@PG comes from the three peaks synergy of starvation treatment, photothermal treatment (PTT), and chemotherapy. This nanoplatform disguised by PLT membrane has significant tumor inhibition ability, good biocompatibility and almost has no side effects in main organs.Conclusion This work broadens the application mode of GOx and shows the new development of a multi-mode collaborative processing system of nanoplatforms based on cell membrane camouflage.

研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Dual-Oxygenation/Dual-Fenton Synergistic Photothermal/Chemodynamic/Starvation Therapy for Tumor Treatment

Hongmei Kang,Lamei Chen,Qin Li,Huan Chen,Liangke Zhang

Due to the complexity of tumor pathogenesis and the heterogeneity of the tumor microenvironment (TME), it is difficult to obtain satisfactory efficacy with a single therapy. In this study, a hyaluronic acid (HA)-modified ruthenium nanoaggregate (RuNA) and glucose oxidase (GOD) -loaded manganese dioxide (MnO2) nanoflowers (MRG@HA) have been prepared. RuNA and MnO2 nanoflowers can generate O2 in TME, alleviating tumor tissue hypoxia. RuNA is a good photothermal agent for high-temperature ablation of solid tumors under infrared laser irradiation. GOD consumes glucose in the presence of O2 and converts it into glucuronic acid and hydrogen peroxide, reducing tumor nutrient supply while promoting Fenton-like reactions of MnO2 nanoflowers and RuNA to produce cytotoxic hydroxyl radicals. MRG@HA can also actively target tumor cells through the affinity of HA and CD44 receptor to improve the antitumor effect. In vitro and in vivo studies have confirmed the synergistic effect of MRG@HA with tumor photothermal/chemodynamic/starvation therapy, showing its great potential for clinical application in tumor therapy.

研究领域: 癌症治疗 · 纳米医学 · 生物医学工程 · 材料科学
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LANGMUIR · 2024 · IF 3.7

Self-Assembled Nanoflowers Realizes Synergistic Sterilization with Photothermal and Chemical Kinetics Therapy

Jing Wu,Shuqing Xiang,Ming Zhang,Ninglin Zhou,Mingqian Wang,Li Li,Jian Shen

Wounds caused by bacterial infections have become a major challenge in the medical field; however, the overuse of antibiotics has led to increased resistance and bioaccumulation. Therefore, it is urgent to develop an antibacterial agent with excellent antibacterial properties and biosafety. Here, we designed an antibacterial platform that combines photothermal and chemical kinetics therapies. Platinum–cobalt (PtCo) bimetallic nanoparticles (NPs) were first prepared, and then PtCo@MnO2 nanoflowers were obtained by adding MES buffer solution and KMnO4 to the PtCo bimetallic nanoparticle suspension using ultrasound. When light strikes metal NPs, they can strongly absorb the photon energy, resulting in photothermal properties. In addition, Pt and Co were used as the oxidase mimics, and MnO2 was used as the catalase mimic. In summary, the photothermal capacity of PtCo@MnO2 nanoflowers with rough surfaces can effectively disrupt the permeability of the bacterial cell membranes. Further, by catalyzing H2O2, PtCo@MnO2 nanoflowers can generate large amounts of hydroxyl free radicals, which can damage bacterial cell membranes, proteins, and DNA. In addition, MnO2 can effectively alleviate the hypoxic environment of the bacterially infected areas and activate deep bacteria, thus achieving the goal of complete sterilization. The in vitro and in vivo results showed that PtCo@MnO2 displayed excellent antibacterial properties and good biocompatibility.

研究领域: 纳米技术 · 材料科学 · 生物医学工程 · 微生物学 · 治疗学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Self-‘cycling, boosting and propelling’ multi-functional nanoplatforms for improving tumor starvation therapy

Qihang Ding,Gongcheng Ma,Yuxin Xie,Hongrong Shi,Qian Bai,Xuechuan Hong,Hui Zhou,Ling Mei,Jong Seung Kim,Shuai Zhang

Starvation therapy, utilizing glucose oxidase (GOx) to deplete glucose and disrupt tumor energy, has shown promise in cancer treatment. However, this approach alone is insufficient to block ATP generation in tumors. Here, we introduce a self-‘cycling, boosting and propelling’ strategy, overcoming the ‘Achilles' heel’ of traditional starvation therapy by regulating the energy supply with CO. The high concentration of H 2 O 2 in the tumor microenvironment reacts with MnO 2 to generate Mn 2+ and O 2 . Mn 2+ catalyzes a Fenton-like reaction to produce hydroxyl radicals ( OH) for chemodynamic therapy and T1-weighted magnetic resonance imaging (MRI), while O 2 further enhances GOx-mediated glucose consumption, producing more H 2 O 2 . This process not only recycles H 2 O 2 but accelerates CO release, disrupting ATP synthesis and inhibiting tumor energy supply. Additionally, the gas released enhances nanoplatform motility, improving tumor penetration and overcoming the limited permeability of conventional nanoparticles. In vitro and in vivo studies demonstrated superior antitumor and antimetastatic efficacy, coupled with excellent biocompatibility. This strategy offers a promising solution to traditional starvation therapy's challenges, with strong potential for clinical translation and transformative cancer treatment.

研究领域: 癌症治疗 · 纳米医学 · 生物化学 · 生物医学工程 · 肿瘤学 · 医学影像
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2021 · IF 5.875

A multifunctional nanoamplifier with self-enhanced acidity and hypoxia relief for combined photothermal/photodynamic/starvation therapy

Shanshan Li,Kunpeng Lin,Peng Hu,Shaochen Wang,Shuang Zhao,Ying Gan,Lei Liu,Shuling Yu,Jiahua Shi

Phototherapies, including photothermal therapy (PTT) and photodynamic therapy (PDT) have been potential noninvasive therapeutic modality with high efficiency, however, there still exist some intrinsic limitations that impede their clinical applications. Herein, taking the advantages of the synergistic effect and high reactivity of manganese dioxide (MnO 2 ) nanosheets and glucose oxidase (GOx), multifunctional [email protected] 2 -MB-GOx nanoamplifier was constructed for enhanced PTT, PDT, and starvation therapy. In tumor microenvironment (TME), MnO 2 nanosheets on the surface of mesoporous polydopamine (MPDA) could react with endogenous hydrogen peroxide (H 2 O 2 ) and generate oxygen (O 2 ) to relieve tumor hypoxia, thus enhancing the efficacy of PDT and GOx catalysis. Glucose consumption under the catalysis of GOx will enhance the acidity of TME and increase intracellular H 2 O 2 concentration, which in turn promotes the production of O 2 by MnO 2 nanosheets, thus forming efficient cascade reaction and maximizing the efficacy of the functional agents. Furthermore, the heat generated by MPDA under the irradiation of 808 nm laser can accelerate chemical reactions, thus further enhancing synergistic therapeutic efficacy. In vitro/vivo results emphasize that enhanced cancer cell death and tumor inhibition are gained by modulating unfavorable TME with the functional nanosystem, which highlights the promise of the synthesized [email protected] 2 -MB-GOx nanomaterial to overcome the limitations of phototherapy.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学 · 药学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Biodegradable Nanocatalyst with Self-Supplying Fenton-like Ions and H2O2 for Catalytic Cascade-Amplified Tumor Therapy

Wenting Li,Xinglu Zhou,Shikai Liu,Jialing Zhou,He Ding,Shili Gai,Rumin Li,Lei Zhong,Huijie Jiang,Piaoping Yang

Therapeutic nanosystems triggered by a specific tumor microenvironment (TME) offer excellent safety and selectivity in the treatment of cancer by in situ conversion of a less toxic substance into effective anticarcinogens. However, the inherent antioxidant systems, hypoxic environment, and insufficient hydrogen peroxide (H2O2) in tumor cells severely limit their efficacy. Herein, a new strategy has been developed by loading the chemotherapy prodrug disulfiram (DSF) and coating glucose oxidase (GOD) on the surface of Cu/ZIF-8 nanospheres and finally encapsulating manganese dioxide (MnO2) nanoshells to achieve efficient DSF-based cancer chemotherapy and dual-enhanced chemodynamic therapy (CDT). In an acidic TME, the nanocatalyst can biodegrade rapidly and accelerate the release of internal active substances. The outer layer of MnO2 depletes glutathione (GSH) to destroy the reactive oxygen defensive mechanisms and achieves continuous oxygen generation, thus enhancing the catalytic efficiency of GOD to burst H2O2. Benefiting from the chelation reaction between the released Cu2+ and DSF, a large amount of cytotoxic CuET products is generated, and the Cu+ are concurrently released, thereby achieving efficient chemotherapy and satisfactory CDT efficacy. Furthermore, the release of Mn2+ can initiate magnetic resonance imaging signals for the tracking of the nanocatalyst.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学
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ACS Nano · 2025 · IF 16

Yeast-Inspired Orally-Administered Nanocomposite Scavenges Oxidative Stress and Restores Gut Immune Homeostasis for Inflammatory Bowel Disease Treatment

Xu Zhang,Huan Yang,Ye He,Dan Zhang,Guifang Lu,Mudan Ren,Yi Lyu,Zhang Yuan,Shuixiang He

Excessive oxidative stress, dysregulated immune homeostasis, and disruption of the intestinal epithelial barrier are crucial features of inflammatory bowel disease (IBD). Traditional treatments focusing solely on inflammation resolution remain unsatisfactory. Herein, a yeast-inspired orally administered nanocomposite was developed. First, the MD@MPDA core was fabricated by integrating manganese dioxide (MnO2) nanozymes onto diallyl trisulfide (H2S prodrug)-loaded mesoporous polydopamine nanoparticles (MPDA). Then, yeast cell wall (YCW) was chosen to encapsulate MD@MPDA, namely, YMD@MPDA. The β-glucan embedded in the YCW shell not only protected the nanocomposite from the harsh gastrointestinal environment but also allowed the targeting enrichment in the inflamed colon. Furthermore, M1 macrophages triggered the intracellular GSH-responsive H2S release in the pathological microenvironment. MD@MPDA effectively alleviated inflammatory responses by MnO2-mediated ROS-scavenging and H2S-participated immunomodulation. The synergistic action contributed to macrophage mitochondrial function restoration and M2 polarization by suppressing NOX4 signaling and p38 MAPK pro-inflammatory signaling. In the mice model of dextran sulfate sodium (DSS)-induced IBD, the multipronged manner of scavenging oxidative stress, remodeling innate and adaptive immune homeostasis, and reshaping gut microbiota caused by YMD@MPDA effectively ameliorated inflammation and restored intestinal barrier functions. Overall, the YMD@MPDA nanocomposite provides a promising codelivery strategy of antioxidative nanozymes and gas prodrugs for the comprehensive management of IBD.

CAS / MDL: 62-31-7 108-67-8 77-86-1
研究领域: 纳米医学 · 胃肠病学 · 免疫学 · 药学
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