Advanced Science
·
2024
·
IF 14.3
Huiyan Du,Ensheng Xu,Yihan Xu,Qingwang Xue,Hongxia Xu,Jibin Song
The development of theragnostic nanosystems integrating FRET (fluorescence resonance energy transfer) imaging and chemodynamic therapy (CDT) for accurate diagnosis and effective treatment of lung tumors is still a big challenge. Herein, a peptide-assembled 3D DNAzyme motor nanodevice is engineered for a self-powered FRET amplifier profiling human neutrophil elastase (HNE) and self-supplied H 2 O 2 enhancing CDT. The nanodevice is prepared by depositing AuNPs on ZIF-8, in which ZIF-8 co-loaded the lysosomal targeting peptide-modified copper peroxides (PCPs) and hairpins (H1, H2, and H3), AuNPs are co-labeled by DNAzyme-peptide (DP) conjugate and H3. In the tumor micro-environment, HNE driven 3D DNAzyme walker followed by an exponential amplification constructed by a synergistic cross-activation between hybridization chain reaction and DNAzyme, generating a self-powered FRET amplifier. The FRET amplifier specifically measures HNE with a sensitivity of 0.026 pM, and successfully images exogenous HNE in living cells and monitors HNE in mouse models. Moreover, the PCPs can target lysosomes, reducing lysosome escape. The self-supplying H 2 O 2 undertaken by PCPs improves the Cu (II)-catalyzed Fenton-like reaction, effectively causing cell apoptosis to inhibit tumor growth. Significantly, the nanodevice successfully screens inhibitors and discriminates the HNE level in normal and lung cancer tissues, suggesting that the nanodevice provides an effective tool for the diagnosis and treatment of lung tumors.
研究领域:
纳米技术
·
癌症诊断与治疗
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Nannan Zheng,Yitong Chen,Lei Jiang,Hongchao Ma
Combined photo-induced cancer therapy (photothermal therapy (PTT) and photodynamic therapy (PDT)) is a promising anti-cancer strategy for its non-invasiveness property. However, severe hypoxia in tumor microenvironment (TME) would weaken the PDT effect and limit the clinical efficiency of PTT/PDT treatment. To solve this problem, denatured BSA-hemin-IR780 (dBHI) was designed and synthesized for anti-cancer treatment in this work. Denatured bovine serum albumin (dBSA) was used as the binding matrix to bind hemin and IR780 via covalent reaction and hydrophobic self-assembly, respectively. The obtained dBHI nanoparticles possess both PTT and PDT effect due to the presence of IR780 in the composites. Moreover, because of the existence of hemin, dBHI also exhibited photo-enhanced Fenton-like catalytic performance, which could decompose H 2 O 2 to form oxygen for improving the PDT effect and generate hydroxyl radical (·OH) for chemodynamic therapy (CDT). Therefore, by using dBHI, synergistic effect of PTT/PDT/CDT combined treatment has been achieved for cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
光疗
·
化学动力学治疗
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 5
·1317-1325
·
IF 7.59
Bengao Zhu,Xuefei Lv,Mengmeng Zhang,Huiying Wang,Senbin Chen,Jintao Zhu
Integrating magnetic resonance imaging (MRI)-targeted diagnosis with synergistic cascade treatments, such as chemo/chemodynamic therapy (CT/CDT), is highly desired for promoting the antitumor performance; however, the rational design of such “all-in-one” nanomedicine is still in its infancy. In this report, using MnO2 coated layered dihydroxide (LDH) as a carrier to load chemotherapy molecule 5-flurouracil (5-FU), a novel tumor microenvironment (TME) regulating nanodrug is formed: LDH/5-FU@MnO2. Combined guidance of CT/CDT and MRI is used to realize synergistic diagnosis and enhanced anti-tumor efficacy. MnO2 is converted into Mn2+ in the presence of reducing agent GSH, the in situ generated Mn2+, not only serves as the chemical fuel for the Fenton reaction, combining H2O2 depletion and ˙OH generation, but can also be used as a nuclear magnetic contrast agent for MRI. Moreover, the tumor acidic environment is able to trigger 5-FU release for initiating chemotherapy in the tumor zone. This “all-in-one” LDH/5-FU@MnO2 nanomedicine integrating multiple treatment modalities and magnetic resonance imaging properties, causes persistent modulation of the TME and exhibits effective antitumor theranostic performance. Such a sophisticated nanomedicine design not only achieves improved CT/CDT antitumor efficiency, but also realizes the activatable magnetic resonance imaging. This strategy combines the merits of each treatment, significantly enhancing the anticancer efficacy, and is anticipated to display promising potentials in the clinical translation plans.
研究领域:
纳米技术
·
癌症治疗
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医学影像
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药学科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 39
·16571-16588
·
IF 7.79
Yu Zhang,Yifeng Yang,Jinsheng Shi,Lili Wang
Weak acidity (6.5–6.9) and limited H2O2 level in the tumor microenvironment (TME) usually impact the therapeutic effect of chemodynamic therapy (CDT) for cancer. A Specific TME promotes the formation of an immunosuppressive microenvironment and results in high rate of recurrence and metastasis of cancer. Fe3O4@ZIF-8/GOx@MnO2 multi-layer core shell nanostructure was constructed as a hybrid nanozyme. After magnetic targeting of the tumor site, the outermost MnO2 shell catalyzed H2O2 in TME to produce O2 and was broken due to the reaction with glutathione. Due to the acid response, the ZIF-8 layer would crack and release glucose oxidase (GOx) and Fe3O4. The generated O2 was utilized by GOx in starvation therapy to consume glucose and produce H2O2 and gluconic acid. The Fenton reaction efficiency of Fe(II) was improved by the increased H2O2 concentration and the enhanced acidity in TME. At the same time, the intrinsic photothermal effect of Fe3O4 upon 808 nm laser irradiation promoted the activity of MnO2 and GOx as oxidase, and Fe(II) as catalase-like, and ablated the primary tumor. Moreover, the hybrid nanozyme can facilitate the transformation of M2-type macrophages to M1-type, and strong systemic antitumor immune effect was induced. A synergy of multiple therapeutic modes including starvation therapy, CDT, photothermal therapy (PTT), and immunotherapy can be realized in the hybrid nanozyme for tumor therapy.
研究领域:
纳米技术
·
癌症治疗
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生物医学工程
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材料科学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 45
·10822-10835
·
IF 7
Mingzhe Liu,Hui Xu,FangFang Zhou,Xiyu Gong,Songwen Tan,Yongju He
The high glutathione (GSH) concentration and insufficient H2O2 content in tumor cells strongly constrict the efficacy of Fenton reaction-based chemodynamic therapy (CDT). Despite numerous efforts, it still remains a formidable challenge for achieving satisfactory efficacy using CDT alone. Herein, an intelligent tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform that integrates GSH-depletion, H2S generation, self-supplied H2O2, co-delivery of doxorubicin (DOX) and Fenton reagent Fe2+ is presented for synergistic triple-enhanced CDT/chemotherapy/H2S therapy. Because the tetrasulfide bond is sensitive to GSH, the nanoplatform can effectively consume GSH, leading to ROS accumulation and H2S generation in the GSH-overexpressed tumor microenvironment. Meanwhile, tetrasulfide bond-induced GSH-depletion triggers the degradation of nanoparticles and the release of DOX and Fe2+. Immediately, Fe2+ catalyzes endogenous H2O2 to highly toxic hydroxyl radicals (˙OH) for CDT, and H2S induces mitochondria injury and causes energy deficiency. Of note, H2S can also decrease the decomposition of H2O2 to augment CDT by downregulating catalase. DOX elicits chemotherapy and promotes H2O2 production to provide a sufficient substrate for enhanced CDT. Importantly, the GSH depletion significantly weakens the scavenging effect on the produced ˙OH, guaranteeing the enhanced and highly efficient CDT. Based on the synergistic effect of triple-augmented CDT, H2S therapy and DOX-mediated chemotherapy, the treatment with this nanoplatform gives rise to a superior antitumor outcome.
研究领域:
纳米技术
·
癌症治疗
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药学
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·Vol. 19
·期 22
·2205511
·
IF 13.3
Yanling Liang,Chuanan Liao,Xinqi Guo,Guanhua Li,Xin Yang,Jing Yu,Jingping Zhong,Ying Xie,Li Zheng,Jinmin Zhao
Noble metal nanozymes hold promise in cancer therapy due to adjustable enzyme-like activities, unique physicochemical properties, etc. But catalytic activities of monometallic nanozyme are confined. In this study, 2D titanium carbide (Ti 3 C 2 T x )-supported RhRu alloy nanoclusters (RhRu/Ti 3 C 2 T x ) are prepared by a hydrothermal method and utilized for synergistic therapy of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) on osteosarcoma. The nanoclusters are small in size (3.6 nm), uniform in distribution, and have excellent catalase (CAT) and peroxidase (POD)-like activities. Density functional theory calculations show that there is a significant electron transfer interaction between RhRu and Ti 3 C 2 T x , which has strong adsorption to H 2 O 2 and is beneficial to enhance the enzyme-like activity. Furthermore, RhRu/Ti 3 C 2 T x nanozyme acts as both PTT agent for converting light into heat, and photosensitizer for catalyzing O 2 to 1 O 2 . With the NIR-reinforced POD- and CAT-like activity, excellent photothermal and photodynamic performance, the synergistic CDT/PDT/PTT effect of RhRu/Ti 3 C 2 T x on osteosarcoma is verified by in vitro and in vivo experiments. This study is expected to provide a new research direction for the treatment of osteosarcoma and other tumors.
研究领域:
癌症治疗
·
纳米技术
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 3
·2202045
·
IF 11.092
Tao Liu,Cheng-Feng Xiong,Lin-Jun Zhang,Guan-Hua Jiao,Hui Shi,Jun Feng,Xian-Zheng Zhang
Doxorubicin (Dox)-mediated generation of reactive oxygen radicals (ROS) for mitochondrial apoptosis is identified as a new cytotoxic mechanism in addition to the well-established one via nuclear DNA replication interference. However, this mechanism contributes far less than the latter to Dox therapy. This newly identified pathway to make Dox therapy function like the combination of chemodynamic therapy (CDT) and chemotherapy-mediated by Dox alone would be amplified. One-pot nanoconstruction (HEBD) is fabricated based on the chemical reactions driven assemblies among epigallocatechin gallate (EGCG), buthionine sulfoximine (BSO) and formaldehyde in aqueous mediums followed by Dox adsorption. Acid tumor microenvironments allow the liberation of EGCG, BSO, and Dox due to the breakage of Schiff base bonds. EGCG component in HEBD is responsible for targeting mitochondria and disrupting mitochondrial electron transport chain (mETC) to compel electrons leakage in favor of their capture by Dox to produce more ROS. EGCG-induced mETC disruption results in mitochondrial respiration inhibition with alleviated hypoxia in tumor cells while BSO inhibits glutathione biosynthesis to protect ROS from redox depletion, further boosting Dox-induced CDT. This strategy of amplifying CDT pathway for the Dox-mediated combined therapy could largely improve antitumor effect, extend lifespan of tumor-bearing mice, reduce risks of cardiotoxicity and metastasis.
研究领域:
药理学
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肿瘤学
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纳米技术
·
治疗学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Han Hu,Shijie Yao,Qi Xu,Xing Cai,Zhimin Mo,Zhe Yang,Wen-Qiu Chen,Qianyuan He,Xiaofang Dai,Zushun Xu
Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) has been developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (·OH), exerting an assistive chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S) leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.
研究领域:
纳米技术
·
癌症治疗
·
光疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Huihui Wang,Xueping Huang,Ran Gao,Ke Li,Dandan Li,Zhuobin Xu,Zemin Ling,Chun Pan,Lizeng Gao,Hao Chen
The intricacy, diversity, and heterogeneity of cancers make research focus on developing multimodal synergistic therapy strategies. Herein, an oxygen (O2) self-feeding peroxisomal lactate oxidase (LOX)-based LOX–Ce6–Mn (LCM) was synthesized using a biomineralization approach, which was used for cascade chemodynamic therapy (CDT)/photodynamic therapy (PDT) combination therapies through dual depletion of lactate (Lac) and reactive oxygen species (ROS) generation. After endocytosis into tumor cells, the endogenous hydrogen peroxide (H2O2) can be converted to O2 by the catalase-like (CAT) activity of LCM, which can facilitate the catalytic reaction of LOX to consume more Lac and alleviate tumor hypoxia to enhance the generation of singlet oxygen (1O2) upon light irradiation. In addition, the H2O2 produced by LOX catalysis and oxidase-like (OXD) activity of LCM can be catalyzed into highly toxic hydroxyl radicals (•OH) via the Fenton-like reaction, enhancing oxidative damage to tumor cells. Both in vitro and in vivo experiments confirmed that LCM significantly promoted ROS accumulation and effectively inhibited tumor growth by inducing tumor cell autophagy under the combined effect of Lac depletion and CDT with PDT. Therefore, integrally designed LCM for reprogramming metabolism and the tumor microenvironment offers a promising multimodal strategy for tumor treatments.
研究领域:
癌症研究
·
生物医学工程
·
诊疗学
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Yiran Zhang,Qingcheng Song,Yueyao Zhang,Jiheng Xiao,Xiangtian Deng,Xin Xing,Hongzhi Hu,Yingze Zhang
Background Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy.Methods and Results A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo.Conclusion The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like osteosarcoma.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2019
·Vol. 17
·期 1
·1-12
·
IF 5.345
Zhao Bin,Zhao Penghe,Jin Zhaokui,Fan Mingjian,Meng Jin,He Qianjun
Background To improve the outcome of cancer treatment, the combination of multiple therapy models has proved to be effective and promising. Gas therapy (GT) and chemodynamic therapy (CDT), mainly targeting the mitochondrion and nucleus, respectively, are two emerging strategy for anti-cancer. The development of novel nanomedicine for integrating these new therapy models is greatly significant and highly desired. Methods A new nanomedicine is programmed by successive encapsulation of MnO 2 nanoparticles and iron carbonyl (FeCO) into mesoporous silica nanoparticle. By decoding the nanomedicine, acidity in the lysosome drives MnO 2 to generate ROS, ·OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of chemodynamic therapy with gas therapy for the first time. Results Acidity in the TEM drives MnO 2 to generate ROS, ∙OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of CDT and CDGT. The co-released ROS and CO do damage to DNA and mitochondria of various cancer cells, respectively. The mitochondrial damage can effectively cut off the ATP source required for DNA repair, causing a synergetic anti-cancer effect in vitro and in vivo. Conclusions The combination of CDT and CDGT causing a synergetic anti-cancer effect in vitro and in vivo. The proposed therapy concept and nanomedicine designing strategy might open a new window for engineering high-performance anti-cancer nanomedicine.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Shuxiang Xu,Shuyi Zhou,Luoyijun Xie,Wenlong Dou,Rongjun Zhang,Bingxia Zhao,Yang Xu,Xuemei Fu,Miaomiao Yuan
Due to the heterogeneous and complex tumor microenvironment (TME), it remains challenging to effectively treat solid tumors with monotherapy. The development of a versatile nanomaterial strategy for synergistic chemodynamic/photodynamic/photothermal therapies has the potential to overcome this challenge. Herein, we designed and synthesized NiS 2 /FeS 2 hybrid nanoparticles (NiS 2 /FeS 2 NPs), which are further modified with polyvinyl pyrrolidone (PVP) to improve their biocompatibility. PVP-NiS 2 /FeS 2 NPs exhibit synergistic activities of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) with multimodal imaging capabilities. With the presence of Fe 2+ /Fe 3+ and Ni 2+ /Ni 3+ redox couples, the PVP-NiS 2 /FeS 2 NPs exhibit GSH peroxidase-like reactivity and trigger Fenton reaction, leading to robust ·OH generation and pyroptosis/ferroptosis after near infared irradiation (NIR). In response to the PVP-NiS 2 /FeS 2 NPs and PVP-NiS 2 /FeS 2 NPs + NIR treatment, the breast tumors formed in the syngeneic BABL/c mice were eliminated and their metastases suppressed by inhibiting the EMT pathway. Consistent with the apparent involvement of these programmed cell death pathways in activating tumor immunity, we demonstrate that PVP-NiS 2 /FeS 2 NPs + NIR can eliminate metastatic tumors in an immune system dependent manner. Therefore, PVP-NiS 2 /FeS 2 NPs represent a promising strategy to treat metastatic breast cancer.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）