JOURNAL OF CONTROLLED RELEASE
·
2025
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IF 11.5
Huijiao Fu,Xiaoqiao Guo,Feng Fang,Cao Zhou,Yuanyuan Chen,Xuanbo Zhang,Bingchen Zhang,Xinran Li,Qiwen Liu,Jie Liu,Wei Chen,Ling Yu,Zhiqiang Yu,Xuefeng Wang
Cisplatin serves as the cornerstone medication in ovarian cancer (OC) chemotherapy; however, numerous resistance factors exist, resulting in unsatisfactory clinical treatment outcomes. Concurrently, OC frequently establishes an immunosuppressive microenvironment, which further exacerbates the challenges of cisplatin chemotherapy. Hence, it is particularly significant to explore a therapeutic approach capable of overcoming cisplatin resistance while reversing the immunosuppressive microenvironment of OC. Here, we synthesized a novel cisplatin polyprodrug (PTP) containing thioketal units, which self-assembled with a stimulator of interferon genes (STING) small-molecule agonist (SR-717) to form redox-smart-responsive PTP@SR-717 nanoparticles (NPs), enabling synergistic chemo-immunotherapy. Specifically, PTP@SR-717 NPs enhanced the anti-tumor effect of cisplatin through three key mechanisms: (i) Pre-target factors: Enhancing intracellular cisplatin uptake and reducing GSH-mediated detoxification to promote platinum accumulation. (ii) On-target factors: Utilizing molecular damage-associated molecular patterns (DAMPs) triggered by cisplatin to activate the STING pathway, thereby synergistically amplifying the STING-TBK1-IRF3 signaling and efficiently triggering an immune response. (iii) Post-target factors: Combining chemotherapy and immunotherapy to harness the immune system for tumor eradication. In conclusion, this study presents an effective approach to addressing the challenges associated with cisplatin in the clinical treatment of OC.
研究领域:
肿瘤学
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药理学
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免疫学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yunhao Wang,Lei Ding,Ziguo Lin,Baolong Li,Di Hu,Shichen Zhang,Shujun Zhou,Yuxiang Ning,Fei Xin,Yunfei Ying,Fukai Zhu,Peiyuan Wang,Yanfeng Wang
Immune checkpoint inhibitors (ICIs) are among the most prominent immunotherapies for cancer and have been approved as first-line treatments for various tumors. Although some patients experience long-lasting responses, the objective response rate (ORR) of ICIs as monotherapy is relatively low due to the complexity of the tumor microenvironment and the heterogeneity of tumors. Maximizing the benefits of this novel therapeutic approach for a greater number of patients remains a research focus in the field of anticancer treatment. Here, we have investigated a novel Pt/Cu Dual-Atom Nanozyme (Pt/Cu DAzyme) which is engineered by the successive growth of metal-nanocrystals on the assembled surfactant templates. This DAzyme can significantly enhance the intracellular copper ion levels in tumor cells, inducing cuproptosis. Additionally, the Pt/Cu DAzyme exhibits excellent dual enzyme catalytic activity as both glutathione oxidase (GSHOx) and peroxidase (POD) activity, which not only reduces glutathione (GSH) levels in tumors to enhance cuproptosis but also converts intracellular H 2 O 2 into •OH to kill tumor cells. Furthermore, the Pt/Cu DAzyme demonstrates a strong photothermal effect, with its enzymatic reactions being enhanced at mildly elevated temperatures. This DAzyme effectively kills tumors and activates the body’s robust immune system, reshaping the tumor immune-suppressive microenvironment and significantly increasing the therapeutic response rate to αPD-L1. It not only achieves complete ablation of primary tumors but also markedly inhibits the progression of distal tumors and distant metastasis. This study aims to develop new combination therapy strategies to enhance the efficacy of ICIs and promote their advancement in the field of cancer immunotherapy.
研究领域:
癌症免疫疗法
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纳米技术
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肿瘤生物学
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免疫学
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分子生物学
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产品关联
DOI
高影响因子
Theranostics
·
2021
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IF 11.556
Han Wu,Hao Xing,Meng-Chao Wu,Feng Shen,Yu Chen,Tian Yang
Background: Conventional therapeutic strategies for advanced hepatocellular carcinoma (HCC) remains a great challenge, therefore the alternative therapeutic modality for specific and efficient HCC suppression is urgently needed. Methods: In this work, HCC-derived extracellular vesicles (EVs) were applied as surface nanocarrier for sequential nanocatalysts GOD-ESIONs@EVs (GE@EVs) of tumor-specific and cascade nanocatalytic therapy against HCC. By enhancing the intracellular endocytosis through arginine-glycine-aspartic acid (RGD)-targeting effect and membrane fusion, sequential nanocatalysts led to more efficient treatment in the HCC tumor region in a shorter period of time. Results: Through glucose consumption as catalyzed by the loaded glucose oxidase (GOD) to overproduce hydrogen peroxide (H 2 O 2 ), highly toxic hydroxyl radicals were generated by Fenton-like reaction as catalyzed by ESIONs, which was achieved under the mildly acidic tumor microenvironment, enabling the stimuli of the apoptosis and necrosis of HCC cells. This strategy demonstrated the high active-targeting capability of GE@EVs into HCC, achieving highly efficient tumor suppression both in vitro and in vivo . In addition, the as-synthesized nanoreactor could act as a desirable nanoscale contrast agent for magnetic resonance imaging, which exhibited desirable imaging capability during the sequential nanocatalytic treatment. Conclusion: This application of surface-engineering EVs not only proves the high-performance catalytic therapeutic modality of GE@EVs for HCC, but also broadens the versatile bio-applications of EVs.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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癌症治疗
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医学影像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-23
·
IF 10.435
Wang Haijun,Jia Dianlong,Yuan Dandan,Yin Xiaolei,Yuan Fengjiao,Wang Feifei,Shi Wenna,Li Hui,Zhu Li-Min,Fan Qing
Background Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O 2 production, which in turn serves as a “radiosensitizer” to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. Results Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (Z Her2 ) mediated cisplatin-loaded mesoporous polydopamine/MnO 2 /polydopamine nanoparticles (Pt@mPDA/MnO 2 /PDA-Z Her2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O 2 . Z Her2 , produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T 1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of Z Her2 . These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. Conclusions The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics. Graphic abstract
研究领域:
纳米医学
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癌症治疗
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分子生物学
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生物医学工程
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放射生物学
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DOI
PubMed
高影响因子
PLoS Pathogens
·
2024
·Vol. 20
·期 1
·e1011926
·
IF 5.5
Zihao Wang,Ziming Jiang,Yu Zhang,Congwei Wang,Zhaoyang Liu,Zhankui Jia,Sudhanshu Bhushan,Jinjian Yang,Zhengguo Zhang
Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections (UTIs) in humans. Moreover, as one of the most common bacterial pathogens, UPEC imposes a substantial burden on healthcare systems worldwide. Epithelial cells and macrophages are two major components of the innate immune system, which play critical roles in defending the bladder against UPEC invasion. Yet, the routes of communication between these cells during UTI pathogenesis are still not fully understood. In the present study, we investigated the role of membrane-bound nanovesicles (exosomes) in the communication between bladder epithelial cells and macrophages during UPEC infection, using an array of techniques such as flow cytometry, miRNA profiling, RNA sequencing, and western blotting. Moreover, our in vitro findings were validated in a mouse model of UPEC-induced cystitis. We found that UPEC infection induced the bladder epithelial MB49 cell line to secrete large numbers of exosomes (MB49-U-Exo), which were efficiently absorbed by macrophages both in vivo and in vitro. Assimilation of MB49-U-Exo induced macrophages to produce proinflammatory cytokines, including tumor necrosis factor (TNF)α. Exposure of macrophages to MB49-U-Exo reduced their phagocytic activity (by downregulating the expression of phagocytosis-related genes) and increased their rate of apoptosis. Mechanistically, we showed that MB49-U-Exo were enriched in miR-18a-5p, which induced TNFα expression in macrophages by targeting PTEN and activating the MAPK/JNK signaling pathway. Moreover, administration of the exosome secretion inhibitor GW4869 or a TNFα-neutralizing antibody alleviated UPEC-mediated tissue damage in mice with UPEC-induced cystitis by reducing the bacterial burden of the bladder and dampening the associated inflammatory response. Collectively, these findings suggest that MB49-U-Exo regulate macrophage function in a way that exacerbates UPEC-mediated tissue impairment. Thus, targeting exosomal -release or TNFα signaling during UPEC infection may represent promising non-antibiotic strategies for treating UTIs.
Urinary tract infections, which are typically caused by uropathogenic Escherichia coli (UPEC), affect over 150 million people each year, worldwide. Because the incidence of antibiotic resistance among UPEC strains is on the rise, urinary tract infections are becoming increasingly challenging to treat using this standard treatment method. Moreover, although the host immune response against UPEC has been intensively studied, the mechanism of communication between bladder epithelial cells and macrophages during UPEC infection remains largely unexplored. Here, we characterized the exosomes released from bladder epithelial cells following UPEC infection and evaluated their impact on macrophages. We demonstrated that bladder tissue destruction following excessive innate immune cell activation during UPEC infection may be driven by exosomes secreted from bladder epithelial cells. We further showed that pharmacologically inhibiting exosomal release from epithelial cells limited macrophage-associated inflammation, innate immune cell infiltration, and histopathological injuries in a mouse model of UPEC-induced cystitis. Collectively, our findings suggest that modulating exosome release represents a promising non-antibiotic therapy for UTIs.
研究领域:
微生物学
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免疫学
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Ying Chen,Zi-Hao Li,Pei Pan,Run-Yao Zeng,Xian-Zheng Zhang
Multiple biological barriers in solid tumors severely restrict the penetration of nanomedicines, which is a main cause for therapeutic failure in traditional tumor treatment. Here, a tumor-specific nanogenerator of peroxynitrite (ONOO–), prepared by loading cisplatin and sodium nitroprusside into poly(d,l-lactide-co-glycolide) polymersomes, was designed to improve drug delivery and enhance tumor chemotherapy. After a cascade of nicotinamide adenine dinucleotide phosphate oxidases catalysis and glutathione reduction, the nanogenerator, namely, PMCS, could selectively induce the generation of ONOO– in tumor. The generated ONOO– could not only strengthen vascular permeability significantly but also improve the accumulation and penetration of PMCS in tumor by activating matrix metalloproteinases-mediated degradation of extracellular matrix. Along with endocytosis, PMCS released cisplatin to induce tumor cell apoptosis. Moreover, free cisplatin liberated from dead cells infected neighboring tumor cells quickly via ONOO–-mediated up-regulated copper transporter 1, further amplifying chemotherapeutic efficacy. This study advances ONOO– as a potent modality to address the main issues of therapeutic delivery, including but not limited to chemotherapy.
研究领域:
药学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-13
·
IF 10.435
Cai Xuzi,Wang Kang-Nan,Ma Wen,Yang Yuanyuan,Chen Gui,Fu Huijiao,Cui Chunhui,Yu Zhiqiang,Wang Xuefeng
Developing novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challenge because of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein, cyclometalated iridium (III) complexes (Ir) with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photon excitation, and mitochondria-targeting capability were designed and further encapsulated into biocompatible nanoparticles (NPs). The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, in vivo experiments demonstrated that the Ir-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 μm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.
研究领域:
生物医学工程
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纳米技术
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癌症治疗
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光学成像
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
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IF 10.633
Xuzi Cai,Si Shi,Gui Chen,Min Zhong,Yuanyuan Yang,Ziyi Mai,Yang Tian,Jinxiu Tan,Lijuan He,Chunhui Cui,Zhiqiang Yu,Xuefeng Wang
Platinum-based chemotherapy is a first-line therapeutic regimen against ovarian cancer (OC); however, the therapeutic potential is always reduced by glutamine metabolism. Herein, a valid strategy of inhibiting glutamine metabolism was proposed to cause tumor starvation and chemosensitization . Specifically, reactive oxygen species-responsive liposomes were developed to co-deliver cisplatin (CDDP) and bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) [ [email protected] LPs]. The [email protected] LPs induced effective tumor cell starvation and significantly sensitized OC cells to CDDP by reducing glutathione generation to prevent CDDP detoxification, suppressing ATP production to avoid CDDP efflux, hindering nucleotide synthesis to aggravate DNA damage induced by CDDP, and blocking mammalian target of rapamycin (mTOR) signaling to promote cell apoptosis. More importantly, [email protected] LPs remarkably inhibited tumor growth in vivo and reduced the side effects. Taken together, this study provided a successful strategy of synergistic chemosensitization and starvation therapy escalating the rate of therapeutic success in OCs. Statement of significance This work proposed a valid strategy of inhibiting glutamine metabolism to cause tumor starvation and chemosensitization. Specifically, ROS-responsive liposomes were developed to co-deliver cisplatin CDDP and BPTES [ [email protected] LPs]. The [email protected] LPs induced effective tumor cell starvation and significantly sensitized OC cells to cisplatin by reducing glutathione generation to prevent cisplatin detoxification, suppressing ATP production to avoid cisplatin efflux, hindering nucleotide synthesis to aggravate DNA damage induced by cisplatin, and blocking mTOR signaling to promote cell apoptosis. More importantly, [email protected] LPs remarkably inhibited tumor growth in vivo and reduced the side effects. Taken together, this study provided a successful strategy of synergistic chemosensitization and starvation therapy escalating the rate of therapeutic success in OCs.
研究领域:
肿瘤学
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药学
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生物医学工程
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化疗
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
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IF 10.383
Meiting Li,Yaqian Zhang,Xiaoge Zhang,Zhuoyin Liu,Junjie Tang,Miao Feng,Baizhu Chen,Dalin Wu,Jie Liu
Sonodynamic therapy (SDT) benefiting from its intrinsic merits, such as noninvasiveness and deep tissue penetrability, is receiving increasing considerable attention in reactive oxygen species (ROS)-based tumor treatment. However, current sonosensitizers usually suffer from low tumor lesion accumulation, insufficient ROS generation efficiency under ultrasound, and non-biodegradability, which seriously impede the therapeutic outcomes. Additionally, it is difficult that SDT alone can completely eradicate tumors because of the complex and immunosuppressive tumor microenvironment (TME). Herein, we simultaneously employ sonosensitive porphyrin building blocks and glutathione (GSH)-responsive disulfide bonds to construct a novel degradable multifunctional porphyrin-based hollow porous organic polymer (POP) nanosonosensitizer (H-Pys-HA@M/R), which combine SDT, “on-demand” chemotherapy, and immunotherapy. Taking the unique advantages of POPs with designable structures and high specific surface area, this H-Pys-HA@M/R nanosonosensitizer can achieve tumor target accumulation, GSH-triggered drug release, and low-frequency ultrasound-activating ROS generation with encouraging results. Furthermore, this multifunctional nanosonosensitizer can effectively evoke immunogenic cell death (ICD) response through the combination of SDT and chemotherapy for both primary and distal tumor growth suppression. Meanwhile, H-Pys-HA@M/R exhibits favorable biodegradation and biosafety. Therefore, this study provides a new strategy for reasonably designing and constructing POP-related sonosensitizers combining SDT/chemotherapy/immunotherapy triple treatment modalities to eradicate malignant tumors.
研究领域:
生物医学工程
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癌症治疗
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纳米技术
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材料科学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
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IF 8.4
Mingqiao Li,Hedan Xu,Nan Zhao,Liangjun Zhang,Haihan Xia,Xiaoxun Zhang,Qiao Li,Min Liao,Qiong Pan,Zeng Yi,Jin Chai
Acute liver injury (ALI) is one of the most important causes of liver failure, and there are no FDA-approved drugs that could therapy late-stage ALI. It has been shown in this study that HA-PEI, a molecule formed by covalently combining HA and PEI, can effectively treat advanced ALI. Through the CD44 receptor, HA-PEI could target the liver actively, with the highest liver-targeting effect confirmed at 1000 K. The underlying mechanism of protection of HA-PEI is by increasing oxygen content, reducing ROS, and maintaining mitochondrial membrane potential. HA-PEI also inhibits the secretion of inflammatory factors and blocks the migration of immune cells to the liver, protecting the hepatocytes not suffer from secondary damage. More importantly, for late-stage ALI, NAC, as the only FDA-approved drug, is completely ineffective, whereas HA-PEI has an excellent therapeutic effect. This work provides a new safe therapeutic agent for ALI, which has a bright application prospect.
研究领域:
药理学
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肝病学
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药物递送系统
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炎症
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氧化应激
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产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Meng Xu,Haidong Zha,Jiamao Chen,Simon Ming-Yuen Lee,Qi Wang,Ruibing Wang,Ying Zheng
Cancer recurrence and metastasis are two major challenges in the current clinical therapy. Here, we synthesized a novel diketopyrrolopyrrole-based photothermal reagent (DCN) with unique J-aggregation-induced redshift to achieve efficient tumor thermal ablation under safe power (0.33 W/cm 2 ). Meanwhile, S-nitroso-N-acetylpenicillamine (SNAP) was co-loaded with near-infrared (NIR)-absorbing DCN in amphiphilic polymers to realize heat-induced massive release of nitric oxide (NO), which could form oxidant peroxynitrite (ONOO – ) to active MMPs, thereby degrading the compact tumor extracellular matrix (ECM) to improve the ablation depth and infiltration of immune cells. Through a facile supramolecular assembly method, the DCN/SNAP nanoparticles were anchored to liquid nitrogen-frozen cancer cells (LNF), achieving enhanced anti-tumor immune responses and effective inhibition of distant tumor and pulmonary metastases after only one treatment. The safety and effectiveness of this supramolecular cell-conjugation platform were verified by 2D/3D cellular experiments and bilateral tumor model, confirming the thermal ablation-gas permeation-antigen presentation therapeutic mode had promising anticancer prospects. This article is protected by copyright. All rights reserved
研究领域:
肿瘤学
·
药学
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生物医学工程
·
免疫疗法
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产品关联
DOI
PubMed
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2023
·
IF 2.7
Xianyang Li,Jingyuan Huang,Xin Wu,Xianling Piao,Danning Lv,Gude Zhang,Dong June Ahn,Chunzhi Cui
In this research, by simultaneously regulating the two major factors affecting the plasmonic enhanced fluorescence (PEF), spectral overlap and the distance between the fluororophores and the noble metal nanoparticles, a significantly enhanced fluorescent signal is achieved. Core-shell nanostructures composed of aspect ratio (AR) adjustable gold nanorods (GNRs) and various thickness of SiO 2 are prepared and the decorated fluorophores are realized optimized PEF. A typical stimuli-responsive conjugated polymer, polydiacetylene (PDA), and a near-infrared (NIR) dye Cy5.5 are selected as fluorophores and their fluorescent signal are enhanced 7.26 and 4.41 times, respectively. Based on the optimized optical properties, a multifunctional antibody modified Mab-Cy5.5-GNRs@SiO 2 is successfully demonstrated the targeting, imaging, and photothermal therapy (PTT) effects on SKOV-3 ovarian cancer cells.
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DOI
高影响因子
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