CHEMISTRY-A EUROPEAN JOURNAL
·
2021
·Vol. 28
·期 1
·e202102885
·
IF 5.236
Yubo Hu,Ke Wang,Cong Ye
Graphical The nanozyme@natural enzyme symbiotic system of Cu 2- x Se−GOx exhibited prominent “four-in-one” cascaded catalytic enzyme activities including catalase, peroxidase, glutathione oxidase and glucose oxidase. The ingenious Cu 2- x Se−GOx could significantly induce the accumulation of reactive oxygen species (ROS) at tumor regions; this results in a tumor microenvironment (TME)-activated “four-in-one” enzyme cascade that is lethal to cervical cancer. All in all, Cu 2- x Se−GOx can act as a high-performance and safe bioactive material for cancer treatment. Cervical cancer, as a common malignant tumor of the reproductive system, seriously threatens women‘s life and health, and is difficult to be cured by traditional treatments, such as surgery, chemotherapy and radiotherapy. Fortunately, tumor microenvironment (TME)-activated catalytic therapy with high efficiency and reduced off-target toxicity has emerged as a novel treatment model. Herein, we designed a “four-in-one” nanozyme and natural enzyme symbiotic system of Cu 2- x Se−GOx for TME-triggered cascaded catalytic enhanced cancer treatment. In response to unique TME, Cu 2- x Se with catalase activity could effectively catalyze over-expressed H 2 O 2 in cancer cells into O 2 . Subsequently, the glucose oxidase (GOx) could deplete intracellular glucose with the assistance of O 2 ; this not only achieves starvation therapy, but also regenerates H 2 O 2 to boost the generation of highly cytotoxic . OH due to the peroxidase activity of Cu 2- x Se. Moreover, although the free-radical scavenger glutathione (GSH) is overexpressed in tumor cells, Cu 2- x Se with glutathione oxidase activity could effectively consume GSH for enhanced ROS production. Thus, the “four-in-one” nanozyme@natural enzyme symbiotic system of Cu 2- x Se−GOx could induce significant ROS accumulation at the tumor regions, thus providing a potential approach for the treatment of cervical cancer.
研究领域:
癌症生物学
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纳米技术
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生物医学工程
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药学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Advances
·
2022
·
IF 9.918
Jiahao Liang,Chao Wang,Jialong Fan,Qian Xie,Zhenlong Yu,Bin Liu,Yan Tian,Jing Ning,Lei Feng,Wei Wang,Xiaochi Ma
Triple-negative breast cancer (TNBC) metastasis is the cause of nearly 90% of breast cancer treatment failures as the side effects of clinical drugs and insufficient efficacy of single-modality therapy. Shikonin (SHK) is a naphthoquinone natural product from the herbal medicine Lithospermum erythrorhizon ., which is widely used for cancer therapy as one kind of Chinese medicine for its significant anti-tumor, anti-metastatic, and anti-inflammatory effects. However, passive targeting of SHK to tumor location in vivo and long-term high dose administration is likely to decrease heart rate and induce drug resistance, which accordingly results in therapeutic failure. Thus, we designed a biomimetic SHK-loading nano-system (Hybrid [email protected] / [email protected] @SHK nanoparticles, HMGPHS NPs) to achieve controlled release and reduced SHK dosage. The prolonged circulation time and higher targeting of the HMGPHS NPs allowed less drug leakage systemically with increased drug concentration at the tumor sites compared to naked ICG/ [email protected] @SHK (GPHS) NPs. Moreover, SHK could down-regulate the expression of COX-2, IL-6, and TNF-α to reduce the photothermal therapy-induced inflammatory response and improve the tumor microenvironment (TME), enabling HMGPHS NPs to significantly inhibit the growth and metastasis of TNBC. We propose that the combination of high efficacy, prolonged circulation, and high targeting of HMGPHS NPs could facilitate the conversion of SHK to clinical application for the effective treatment of TNBC.
研究领域:
肿瘤学
·
药剂学
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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Benjin Chen,Liang Xiao,Wanni Wang,Lingling Xu,Yechun Jiang,Guoqiang Zhang,Lin Liu,Xiaohu Li,Yongqiang Yu,Haisheng Qian
Radiotherapy efficacy was greatly limited by hypoxia and overexpression of glutathione (GSH) in the tumor microenvironment (TME), which maintained the immunosuppressive microenvironment and promoted DNA repair. In this work, 4T1 cell membrane-coated Bi2–xMnxO3 nanospheres have been achieved via a facile protocol, which showed enhanced therapeutic efficacy for a combination of radiotherapy and immunotherapy. Bi2–xMnxO3 nanospheres showed appreciable performance in generating O2 in situ and depleting GSH to amplify DNA damage and remodel the tumor immunosuppressive microenvironment, thus enhancing radiotherapy efficacy. Cancer cell membrane-coated Bi2–xMnxO3 nanospheres (T@BM) prolonged blood circulation time and enriched the accumulation of the materials in the tumor. Meanwhile, the released Mn2+ could activate STING pathway-induced immunotherapy, resulting in the immune infiltration of CD8+ T cells on in situ mammary tumors and the inhibition of pulmonary nodules. As a result, approximately 1.9-fold recruitment of CD8+ T cells and 4.0-fold transformation of mature DC cells were observed compared with the phosphate-buffered saline (PBS) group on mammary tumors (in situ). In particular, the number of pulmonary nodules significantly decreased and the proliferation of pulmonary metastatic lesions was substantially inhibited, which provided a longer survival period. Therefore, T@BM exhibited great potential for the treatment of 4T1 tumors in situ and lung metastasis.
研究领域:
癌症治疗
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纳米医学
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免疫学
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Zhao Wei,Jingyi Liu,Yuanbo Jia,Meng Lei,Songbai Zhang,Pan Xi,Yufei Ma,Min Zhang,Jinlu Ma,Lin Wang,Hui Guo,Feng Xu
The fiber structures of tumor microenvironment (TME) are well-known in regulating tumor cell behaviors, and the plastic remolding of TME has recently been suggested to enhance tumor metastasis as well. However, the interrelationship between the fiber microarchitecture and matrix plasticity are inextricable by existing in vitro models. The individual roles of fiber microarchitecture and matrix plasticity in tuning tumor cell behaviors remain elusive. In this study, we develop a interpenetrating collagen-alginate hydrogel platform with independently tunable matrix plasticity and fiber microarchitecture through an interpenetrating strategy of alginate networks and collagen I networks. With this hydrogel platform, we demonstrate that tumor cells in high plasticity hydrogels are more extensive and aggressive than in low plasticity hydrogels and fiber structures only has influence in high plasticity hydrogels. We further elucidate the underlying mechanisms through analyzing the distribution of forces within the matrix and tracking the focal adhesions (FAs) and find that highly plastic hydrogels can activate the FAs formation, whereas the maturation and stability of FAs are dominated by fiber dispersion. This study not only establishes new ideas on how cells interact with TME cues but also would help to further finely tailor engineered hydrogel platforms for studying tumor behaviors in vitro. This article is protected by copyright. All rights reserved
研究领域:
生物材料
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生物力学
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癌症生物学
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细胞生物学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Yuanqi Yang,Qingqing Xu,Wei Gu,Kaisheng Nan,Siyu Chen,Siling Wang,Jinghai Zhang,Qinfu Zhao
Photodynamic therapy (PDT) has witnessed remarkable progress in recent years owing to its specific properties. Given that the antioxidation system of tumor microenvironment (TME) adversely affects treatment outcomes, powerful TME modulators can significantly resolve the limitation of PDT. Herein, we developed a PEG-modified Cu 2+ -doped hollow mesoporous carbon nanozyme (CHC-PEG) and loaded insoluble photosensitizer IR780 into its pores and cavities to construct the multifunctional nano-system IR780/CHCP. CHC-PEG nanozyme could perform photothermal therapy (PTT) effect and protect IR780 from aggregation-caused quenching (ACQ) effect, while exerting peroxidase (POD)-mimetic activity and the ability of consuming glutathione (GSH) to achieve oxidative stress-augmented PDT effect. When exposed to near-infrared (NIR) light, IR780 was stimulated to produce singlet oxygen ( 1 O 2 ) and CHC-PEG could increase the temperature of TME to exert stronger POD-mimetic activity for producing more hydroxyl radicals ( OH), therefore the IR780/CHCP nano-system exhibited remarkable tumor growth inhibition. Benefited by the enhanced synergistic effect, IR780/CHCP exhibited remarkable in vivo tumor growth inhibition, with the tumor inhibition rate of 93 %, and had no significant effect on major organs. Above all, IR780/CHCP could resist the antioxidant system in TME to enhance the level of oxidative stress, thereby enabling effective anti-tumor therapy. This study introduced a novel strategy to effectively promote the synergistic PTT/PDT effect by the enhanced oxidative stress.
研究领域:
癌症治疗
·
纳米医学
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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
CANCER IMMUNOLOGY IMMUNOTHERAPY
·
2025
·Vol. 74
·期 3
·1-17
·
IF 5.1
Han Tianci,Guo Xiaoqi,Xie Junwei,Tong Wei,Zhang Liang
Objective Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high metastasis rate and a poor prognosis. ETS variant transcription factor 1 (ETV1) plays an important role in multiple malignancies. However, its function in ESCC progression and tumor microenvironment (TME) remains to be explored. In this study, we characterized the role of ETV1 in ESCC process and TME. Methods Gene expression and immune infiltration in ESCC samples from the Cancer Genome Atlas (TCGA) were analyzed. The expression of ETV1 in clinical samples was detected by real-time PCR, western blot and immunohistochemistry staining. Cell growth was detected by CCK-8 and colony formation assays. Macrophage phenotypes were determined using flow cytometry. Immunofluorescence double staining was used to detect the tumor-associated macrophage (TAM) infiltration. The tumor volume was recorded and weighed. Transcriptional activity was measured using dual-luciferase assay, chromatin immunoprecipitation (ChIP) assay and DNA pull-down assay. Results In this study, through analysis of ESCC samples from TCGA database and the clinic, we noticed that ETV1 was highly expressed in ESCC tumor tissues and was associated with TAM infiltration. Overexpression of ETV1 promoted ESCC cell proliferation in vitro and xenograft tumor growth in nude mice, while ETV1 knockdown elicited the opposite effects. Furthermore, ETV1 upregulation in tumor tissues was found to drive M2 macrophage infiltration both in vitro (transwell assays) and in vivo (xenograft tumor models). C–C motif chemokine ligand 2 (CCL2), a key factor inducing M2 macrophage polarization, was also found to be elevated in ESCC tumor tissues. Mechanism study demonstrated that ETV1 facilitated M2 macrophage infiltration via the transcriptional modulation of CCL2. In addition, the cause of the changes in ETV1 activity and expression was investigated. The E2 small ubiquitin-like modifier (SUMO) binding enzyme UBC9 increased ETV1 activity and expression, indicating the presence of SUMO modification in ETV1. Conclusions Our data deciphered the mechanism of ETV1-mediated M2 macrophage infiltration in the TME of ESCC, which has important implications for the development of novel prognostic and therapeutic targets to optimize current therapies against ESCC.
研究领域:
肿瘤学
·
免疫学
·
转录调控
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Tang Lei,Sun Qinyi,Li Mengyuan,Yu Xiaoxiao,Meng Jinguo,Zhang Yun,Ma Yuxiao,Zeng Aizhong,Li Zhuolan,Liu Yuanyuan,Xu Xinyu,Guo Wei
Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs.Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods.Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model.Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.
研究领域:
肿瘤学
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免疫治疗
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分子生物学
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癌症研究
✓ 已验证
DOI
高影响因子
ACS Nano
·
2020
·
IF 14.588
Benjin Chen,Chenyang Zhang,Wanni Wang,Zhaoyou Chu,Zhengbao Zha,Xiaoyan He,Wei Zhou,Tao Liu,Hua Wang,Haisheng Qian
Specific cytotoxicity for catalytic nanomedicine triggered by the tumor microenvironment (TME) has attracted increasing interest. In this work, we prepared AgBiS2 hollow nanospheres with narrow bandgaps via rapid precipitation in a weakly polar solvent, which lowered the intrinsic energy gap for the active production of highly reactive hydroxyl radicals (•OH), especially in the TME. The as-prepared AgBiS2 hollow nanospheres exhibited enhanced optical absorption and high photothermal conversion efficiency (44.2%). In addition, the hollow structured AgBiS2 nanospheres were found to have a peroxidase-mimicking feature to induce cancer cell-specific cytotoxicity while exhibiting negligible cytotoxicity toward normal cells, which might be attributed to the efficient production of highly reactive •OH originating from the overexpression H2O2 in the TME caused by surface catalysis. In particular, the cancer cell-specific cytotoxicity of the nanospheres was greatly enhanced both in vitro and in vivo upon irradiation with a near-infrared (NIR) laser (808 nm). The above-mentioned features of the hollow structured AgBiS2 will make it a promising candidate for tumor therapy.
研究领域:
纳米医学
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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
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 17
·3677-3688
·
IF 6.331
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
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Di Chuan,Huan Hou,Yuelong Wang,Min Mu,Jinglun Li,Yangmei Ren,Na Zhao,Bo Han,Haifeng Chen,Gang Guo
Due to the hypoxic state of the tumor microenvironment (TME), photodynamic therapy (PDT) suffers from insufficient ROS production. The metal-polyphenol network-mediated Fenton reaction can generate reactive oxygen species (ROS) by consuming H 2 O 2 in TME, improving the inadequate ROS generation problem of PDT. Therefore, synergistic therapy combining PDT and Fenton response-based CDT is a promising approach for cancer treatment. Herein, a metal-polyphenol nanocomposite was deposited with gallic acid grafted hyaluronic acid and Fe 3+ to contrast a Ce6 nano-delivery system ( [email protected] NPs) for melanoma synergistic therapy. [email protected] NPs could be used as a Fenton reagent to induce the ·OH production and enhance the PDT effect of Ce6 to a certain extent. After 4 h of cellular uptake, the fluorescence intensity of Ce6 in the [email protected] NPs group was higher than 3 times that in the Ce6 group. The intracellular ROS generation level of the [email protected] NPs (L) group combining CDT and PDT was higher than that of the Ce6 group and [email protected] NPs group. In vitro and in vivo anti-melanoma studies show that [email protected] NPs (L) group exhibited better anti-melanoma than other groups. Together, [email protected] NPs provide a promising synergistic treatment potential for melanoma.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Research
·
2024
·
IF 8.1
Ding Wang,Cheng-Jie Qiu,Yaoqing Chu,Anzhuo Zhang,Ran Huang,Si-Jian Pan,Lianjiang Tan
Lung cancer remains a great threat to human health despite the rapid development of various therapeutic methods. Chemotherapy continues to be the most commonly employed treatment for lung cancer; however, it often suffers from low drug delivery efficiency and severe side effects. To enhance the therapeutic efficacy of chemotherapy, we developed a novel strategy that integrates tumor vasculature normalization with the co-delivery of therapeutic agents. This strategy employs a diblock polymeric vesicle with a reduction-sensitive linkage. Paclitaxel (PTX) is encapsulated in the bilayer, while an acid-sensitive nitric oxide (NO) precursor, DETA NONOate, and zinc oxide nanoparticles (ZnO NPs) are loaded into the central cavity. The resulting nanosystem, (ZnO,NONO)@Ves-PTX, is designed to release NO under the acidic conditions typical of the tumor microenvironment (TME) and intracellular environment. The released NO in the TME inhibits angiogenesis, thereby facilitating the delivery and distribution of therapeutic agents. Upon internalization by tumor cells, (ZnO,NONO)@Ves-PTX decomposes in response to intracellular glutathione (GSH), releasing the loaded agents. DETA NONOate and ZnO NPs generate NO and Zn2+ ions, respectively, at the intracellular pH, which synergistically inhibit tumor growth alongside PTX. This combined therapeutic approach demonstrated remarkable potential in improving the chemotherapeutic efficacy for lung cancer, offering a promising direction for future cancer treatments.
研究领域:
肿瘤学
·
药理学
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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Qi Meng,Jia Tan,Weifang Tong,Changxiao Chen,Zhendong Liu,Sainan Liu,Meifang Wang,Ziyong Cheng,Binbin Ding,Ping'an Ma,Jun Lin
Chemodynamic therapy (CDT) is an antitumor strategy based on the Fenton response. However, the mild acidity in the tumor microenvironment (TME) limits the efficiency of the Fenton response. Lactic acid has the potential to regulate pH in TME by regulating its metabolism. α-cyano-4-hydroxycinnamic acid (CHCA) can block lactate transport and induce lactate accumulation in cells, thus enhancing intracellular acidity. Nevertheless, CHCA is insoluble in water and the existing nanodrug delivery systems have complex synthesis and low drug-loading. Herein, we use Fe 3+ and CHCA to form ultrahigh drug-loading supramolecular nanoparticles (FC NPs) by an ultrafast self-assembly strategy at room temperature for only 5 min. Polyethylene glycol (PEG) modified FC (FCP) NPs undergo lactate metabolism regulation-enhanced CDT in tumor cells to generate toxic hydroxyl radicals to induce apoptosis. Besides, glutathione is consumed and glutathione peroxidase 4 is down-regulated to induce ferroptosis due to the oxidation of Fe 3+ . In vitro and in vivo experiments show FCP induced synergetic effect of CDT and ferroptosis as well as the excellent therapeutic effect compared with either CHCA or Fe 3+ alone. We believe that the ideal design of the CHCA supramolecular nanosystem will provide more revelations on the future research about CDT and lactate metabolism therapy.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物化学
✓ 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）