ADVANCED MATERIALS
·
2025
·
IF 26.8
Kun Shang,Dongsheng Tang,Minhui Cui,Hongyi Hou,Bing Xiao,Jinjian Liu,Ruoshi Zhang,Rui Kuai,Jianfeng Liu,Haihua Xiao,Fan Huang,Jianliu Wang
Cisplatin is a first-line, broad-spectrum anti-tumor drug used to treat various types of cancer. However, immune-suppressive tumor microenvironments (TME) are often induced by cisplatin. Here, a first synthetic high-density lipoprotein (sHDL) nanodisc, referred as sHDL@Pt, is engineered to load a Pt(IV) prodrug (C2-Pt(IV)-C12), inducing a 2.2-fold increase in dsDNA release compared to cisplatin. This further activates the innate immune system through the cGAS-STING pathway. Using near-infrared II fluorescence imaging and single photon emission computed tomography imaging technology, it is found that sHDL@Pt can be effectively accumulated in tumor sites. The sHDL@Pt can induce severe DNA damage, which subsequently results in a more pronounced activation of the cGAS-STING pathway, further promoting dendritic cell maturation and T cell proliferation, triggering strong cytotoxic T lymphocyte responses, and inhibiting tumor growth. This work introduces a novel approach for delivering Pt(IV) prodrug that effectively initiates and activates innate immunity through the activation of the cGAS-STING pathway.
研究领域:
纳米医学
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肿瘤学
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免疫治疗
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药理学
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生物工程
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产品关联
DOI
PubMed
高影响因子
HYDROMETALLURGY
·
2023
·
IF 4.7
Haitao Zhou,Kun Huang
In conventional liquid-liquid extraction, Pt(IV) and Pd(II) chloride complex anions PtCl 6 2− and PdCl 4 2− in concentrated hydrochloric acid cannot be separated using simple amine extractants according to the ion association mechanism based on the thermodynamic difference in the interaction of their inner sphere coordinated chloride ions with protonated amine. This study exhibits a novel strategy for enhancing the separation of PtCl 6 2− and PdCl 4 2− anions using thin-layer organic membrane-based laminar flow (TOMLF) extraction by controlling the acidified primary amine N1923 (A-N1923) molecular orientation on the surface of concentrated hydrochloric acid with a laminar shear flow. Experiments revealed that the separation selectivity is primarily determined by the interaction of A-N1923 molecules with the outer sphere-bound water molecules around PtCl 6 2− and PdCl 4 2− anions, and is easily controlled by regulating the A-N1923 molecular orientation on the surface of laminar flow. It is a new phenomenon that has not been previously documented. The evolution of A-N1923 molecular orientation and complexation sites induced by laminar shear flow would result in a controllable spatial geometry recognition, therefore promoting or inhibiting the separation of PtCl 6 2− and PdCl 4 2− anions in concentrated hydrochloric acid. This work is expected to provide new insight into the development of hydration-sphere coordination strategies based upon shear-switch laminar flow for controllable host-guest molecule recognition at a flowing liquid-liquid interface.
研究领域:
化学工程
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材料科学
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分析化学
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物理化学
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Jun Li,Qiang Zhang,Hao Yang,Wenli Lu,Yulong Fu,Yingcai Xiong,Xuan Wang,Tianming Lu,Yanlin Xin,Zejuan Xie,Weichao Chen,Guoqiang Wang,Yuanyuan Guo,Ruogu Qi
Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2022
·Vol. 14
·期 25
·2541-2548
·
IF 3.532
Lixia Su,Yonghuan Su,Bingqian Liu
A new ratiometric electrochemical strategy for immobilization-free detection of Escherichia coli (E. coli) was constructed by using a capture DNA-polyaniline/copper ferrite nanoparticles/graphene oxide (cDNA-PANI/CuFe2O4/GO) composite as capture probes, which has a high specific surface area and good magnetic properties. Then trigger DNA/Au nanoparticles (tDNA/Au NPs) were used as signal amplification labels, and Pt (IV) and Fe (III) were chosen as the signal probes. In the presence of targets, the sandwich format among cDNA-PANI/CuFe2O4/GO, E. coli and auxiliary DNA (aDNA) was realized by using the aptamer recognition system. Then, the tDNA/Au binding could be anchored on the sandwich format due to the principle of base complementation between unpaired aDNA and tDNA. And the unbounded tDNA of tDNA/Au NPs could bind an amount of Pt (IV). After separation using a magnet, a handful of unbound Pt (IV) which remained in the supernatant reacted with a large number of Fe (III) ions, leading to a markedly increased IFe(III)/IPt(IV) value. Oppositely, the sandwich format could not appear in the absence of targets, and even the tDNA/Au could not be immobilized on it. So, the redox reaction between a large amount of Pt (IV) residue in the supernatant and Fe (III) was significantly successful, causing a low IFe(III)/IPt(IV) value. Under optimal conditions, we found that IFe(III)/IPt(IV) was linearly related to the logarithmic E. coli concentration with a low limit of detection (1.862 × 103 cfu mL−1). This devised ratiometric electrochemical method may develop into a powerful and effective means for the detection of E. coli in real samples, which may also be developed as a universal tool for another microorganism.
研究领域:
分析化学
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电化学
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微生物学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Yangyang Wang,Xiaoxia Liu,Annie Yang,Ping Lv,Lixin Zhang,Yongnian Li,Yanzhao Yang
Selective recovery of gold and platinum from secondary resources is of great significance under the crisis of resource shortage. Hence, the optimal extractant 1-(2-(dimethylamino) ethyl)-4-methyl-piperazin bis(trifluoromethylsulfonyl)imide ([C 6 -Et-TMEDA-PIP][Tf 2 N] 2 ) was synthesized and screened out from five piperazine-based ionic liquids (ILs) to construct an IL-water system for Au(III) and Pt(IV) extraction. ILs have high hydrophobicity and low viscosity at room temperature, which can be used as both extractant and hydrophobic phase. The effects of IL dosage, metal concentration and acidity on the extraction efficiency were investigated. Under the optimal conditions, the extraction efficiency of 98.5% (Au(III)) and 97.5% (Pt(IV)) can be achieved. The anion exchange mechanism was verified through the combination of Ultraviolet visible spectroscopy (UV–vis), Nuclear magnetic spectra (NMR) and quantum chemical calculations. Besides that, the two-factor optimization of the extractant dosage and HCl concentration was carried out by Response surface methodology (RSM), and the effective separation of Au(III) and Pt(IV) was successfully achieved. Au(III)/ Pt(IV) was extracted into the IL phase as [Et-TMEDA-PIP + ][AuCl 4 - ] and can easily be stripped by reduction to Au(0)/Pt(Ⅱ) with H 2 C 2 O 4 /CS(NH 2 ) 2 -HCl, and each extraction ability maintained after 5 turns of extraction cycle experiments. Since the excellent behaviors showed in the multi-metal selective extraction and cycle experiments, the [C 6 -Et-TMEDA-PIP][Tf 2 N] 2 was regarded as the most potential system for Au(III) and Pt(IV) recovery from HCI medium.
研究领域:
化学
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材料科学
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环境科学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Zhe Li,Xiao-Meng Liu,Fei Tan,Jia-Qian Wang,Xin Qiao,Yu-Kuan Feng,Jing-Yuan Xu,Ji-Hui Hao
Convincing evidence revealed that some platinum-based drugs could stimulate immunological recognition, thereby inducing immunogenic cell death (ICD). Indoleamine-2,3-dioxygenase (IDO) is overexpressed in tumors, which caused exhaustion of tryptophan (T-cell energy) and constructed an immunosuppressive tumor microenvironment. Herein, considering IDO inhibition to improve chemotherapy, a series of IDOi-Pt(IV) prodrugs were designed to not only target DNA and IDO but also facilitate tumor-antigen exposure and immunomodulation. The optimal IDOi-Pt(IV) prodrugs (named compound 10) significantly enhanced intracellular accumulation 22.4-fold and cytotoxicity 61.75-fold superior to cisplatin in HeLa cells. Moreover, immunofluorescence and enzyme-linked immunosorbent assays revealed that 10 induced reactive oxygen species-mediated endoplasmic reticulum stress and secretion of damage-associated molecular patterns, thereby presenting ICD effects. Molecular docking, enzyme inhibition, and Western blot assays demonstrated that 10 could effectively inhibit IDO1 and reverse immunosuppression, as further verified by mixed leukocyte reactions. In vivo tests showed that 10 exhibited high-efficiency and low-toxicity antitumor effects compared to cisplatin, presenting successful chemoimmunotherapy.
研究领域:
肿瘤学
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免疫学
·
药理学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2022
·Vol. 9
·期 14
·3470-3483
·
IF 7.779
Xiao-Meng Liu,Zhe Li,Xin-Rui He,Rui-Ping Liu,Zhong-Ying Ma,Xin Qiao,Shu-Qing Wang,Jing-Yuan Xu
The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvant therapy drugs for early stages of breast cancer. In this paper, we employed the FDA-approved aromatase inhibitor aminoglutethimide (AG) to design and prepare a new class of multi-targeting Pt(IV) prodrugs (aminoplatins 1–3) by utilizing the targeting, estrogen-manipulating, and chemo-sensitizing effects of the aromatase inhibitor. Aminoplatin 3, as a representative, exhibited an enhanced anticancer activity up to 190-fold greater than the parent Pt(II) drug cisplatin, and 3 had less toxicity to normal cells, displaying higher anticancer efficacy and a superior therapeutic index compared to those of cisplatin. Moreover, aminoplatin 3 could enhance intracellular accumulation, induce remarkable DNA damage, inhibit migration and metastasis, and result in S phase cell cycle arrest and apoptosis in ER-positive MCF-7 cells. Besides, molecular docking results showed that 3 simultaneously occupies the heme iron-binding domain and the ASD-binding site of aromatase by a highly efficient dual-binding pattern to aromatase, which further displayed a striking anti-estrogenic effect by significant downregulation of CPY19A1 and ERα in ER-positive MCF-7 cells. Most strikingly, our in vivo anticancer evaluation data also provided evidence that 3 effectively inhibited tumor growth and attenuated kidney toxicity compared to cisplatin in MCF-7 xenografted BALB/c nude mice. Our results suggest that the anticancer activity of aminoplatins is mechanistically distinct from that of the conventional platinum drugs, and modifying platinum drugs with aromatase inhibitors may represent an improved modality for the treatment of advanced postmenopausal breast cancer.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2015
·
IF 8.557
Song Shen,Chun-Yang Sun,Xiao-Jiao Du,Hong-Jun Li,Yang Liu,Jin-Xing Xia,Yan-Hua Zhu,Jun Wang
As part of HCC tumor cellularity , cancer stem cells (CSCs) are considered a major obstacle to eradicate hepatocellular carcinoma (HCC), which is the third most common cause of cancer-related death worldwide, and the accumulation of chemotherapeutic drug-resistant CSCs invariably accounts for poor prognosis and HCC relapse. In the present study, we explored the efficacy of co-delivery of platinum drug and siRNA targeting Notch1 to treat CSCs-harboring HCC. To overcome the challenging obstacles of platinum drug and siRNA in the systemic administration, we developed a micellar nanoparticle (MNP) to deliver platinum(IV) prodrug and si Notch1 , hereafter referred to as Pt(IV) MNP/si Notch1 . We demonstrated that Pt(IV) MNP/si Notch1 was able to efficiently deliver two drugs into both non-CSCs and CSCs of SMMC7721, a HCC cell line. We further found that siRNA-mediated inhibition of Notch1 suppression can increase the sensitivity of HCC cells to platinum drugs and decrease the percentage of HCC CSCs, and consequently resulting in enhanced proliferation inhibition and apoptosis induction in HCC cells in vitro . Moreover, our results indicated that the combined drug delivery system can remarkably augment drug enrichment in tumor tissues, substantially suppressing the tumor growth while avoiding the accumulation of CSCs in a synergistic manner in the SMMC7721 xenograft model.
研究领域:
肿瘤学
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药学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
·
2025
·Vol. 14
·期 1
·120674
·
IF 7.2
Meng Cheng,Wenjing Liu,Chenxi Yang,Qian Jia,Ziyang Yang
Developing efficient materials capable of selectively extracting platinum from secondary resources represents a critical step toward addressing the global shortage of platinum resources and environmental concerns. In this study, we report the rational design and successful synthesis of a novel polymer-supported quaternary ammonium ionic liquid (CPR-BDEA) for the selective separation and recovery of platinum (Pt(IV)). CPR-BDEA exhibited an impressive maximum adsorption capacity 411.5 mg/g (pH=4) and maintained excellent selectivity for Pt(IV) even in the competitive multi-ion systems. Its practical applicability was validated by effective Pt(IV) capture from real leaching solutions derived from e-waste and spent automotive catalyst. Furthermore, CPR-BDEA exhibited excellent regenerability and still maintained a high recovery efficiency for Pt(IV) after five cycles. Finally, with the aid of various characterization technologies and density functional theory (DFT), the adsorption mechanism between CPR-BDEA and Pt(IV) was revealed detailly, including electrostatic attraction, hydrogen bonds and van der Waals between the side chain of CPR-BDEA and Pt(IV), ion exchange and other interactions. It is expected that this study would provide fundamental insights into the design and preparation of quaternary ammonium salt functionalized materials and contribute to the development of sustainable strategies for the selective separation of precious metals from secondary resources.
研究领域:
环境化学
·
材料科学
·
湿法冶金
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可持续资源回收
·
离子液体
✓ 已验证
产品关联
DOI
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Xiao-Yan Yang,Zi-Qiang Luo,Dan Fang,Quan-Bing Chen,Na Peng,Hong-Ming Fang,Tao Zou
Chemotherapy (CT) can significantly inhibit tumor growth, metastasis, and recurrence during cancer therapy. People have widely used platinum drugs in cancer treatment. However, as most chemotherapeutic drugs, platinum drugs still have shortcomings such as poor solubility, low cell uptake, nonspecific distribution, multidrug resistance, and adverse side effects. Therefore, we synthesized hollow copper sulfide (CuS) nanocubes with photothermal and photodynamic properties as carriers for Pt(IV) drugs. Hollow CuS nanocubes have attracted considerable interest in the field of cancer photothermal therapy (PTT) using multiple biological windows. Under near-infrared (NIR) laser irradiation, Cu2+ can be reduced into Cu+ in the presence of hydrogen peroxide in the tumor microenvironment. The resulting Cu+ can be used for photodynamic therapy (PDT), which can perform a Fenton-like reaction under acidic conditions (pH 5.5–6.5) and catalyze hydrogen peroxide to produce ·OH in the tumor microenvironment. In addition, compared with Pt(II) drugs, Pt(IV) drugs not only have lower systemic toxicity but also consume glutathione (GSH), thereby increasing reactive oxygen species (ROS) levels in tumor cells and effectively promoting PDT. In this study, we oxidized ethylenediamine platinum chloride to its tetravalent state, loaded the Pt(IV) complexes using hollow CuS nanocubes, and modified the surfaces of the nanoparticles with PEG to improve the EPR effect. The Pt(IV)-loaded hollow CuS nanocubes modified with PEG (Pt(IV)-CuS@PEG) are expected to be used for tumor chemo/photothermal/photodynamic therapy.
研究领域:
生物医学工程
·
癌症治疗研究
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2022
·
IF 4.336
Zhe Li,Xiao-Jing Ding,Xin Qiao,Xiao-Meng Liu,Xin Qiao,Cheng-Zhi Xie,Rui-Ping Liu,Jing-Yuan Xu
Combination of immune- and chemo-therapy has become a new trend in cancer treatment. Food and Drug Administration (FDA)-approved immune-modulatory agent, thalidomide , can modulate the related proteins of upstream signaling pathway of programmed cell death-ligand 1 (PD-L1), including nuclear transcription factor κ B (NF- κ B), hypoxia inducible factor-1α (HIF-1α), epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3), all acting as key antitumor target proteins. In this work, we conjugated thalidomide with oxidized cisplatin to construct multi-functional Pt(IV) prodrugs , named thaliplatins 4 – 6 , to investigate the anti-tumor effect of immuno- and chemo-therapy. Among them, thaliplatin 6 exerted remarkable cytotoxicity against the tested cancer cell lines, showing 15–26 and 9–20 times higher IC 50 values than those of single cisplatin or the combination of cisplatin + thalidomide, respectively. Moreover, thaliplatin 6 could rapidly accumulated into cells, markedly triggered DNA damage, and induced cell S phase arrest and apoptosis, as well as inhibited cell migration and invasion in breast carcinoma cell line (MCF-7). Fluorescent confocal and western blotting experiments proved that 6 significantly regulated NF- κ B, EGFR, HIF-1 α and phosphor-signal transducer and activator of transcription 3 ( p -STAT3), and simultaneously inhibited PD-L1 expression to interrupt programmed cell death 1 (PD-1)/PD-L1 signaling pathway, suggesting a synergistic action of cisplatin and thalidomide. Most strikingly, in vivo tests indicated that 6 effectively decreased tumor growth with no observable systemic toxicity, being superior to the anticancer efficacy of cisplatin.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Xiao Kuang,Yuting Hu,Dongxu Chi,Haolin Zhang,Zhonggui He,Yiguo Jiang,Yongjun Wang
A surge of platinum(IV) compounds are utilized or investigated in cancer treatment but their therapeutic outcomes have been greatly compromised by remaining adverse effects and limited antitumor performance, attributable to nonspecific distribution and insufficient activation in tumor site. Herein, we designed a series of disulfide bond introduced Pt(IV)-lipid prodrugs with different branch length, all of which are able to self-stabilize into nanomedicine and be activated by high intracellular glutathione (GSH) level. The impact of precise modification of these prodrugs on their assembly stability, pharmacokinetics and cytotoxicity was probed to establish a connection between chemical structure and antiproliferation efficiency. With optimal assembly manner and delivery efficacy, the longest axial branched Pt(IV) prodrug CSS18 exhibited the most impressive therapeutic outcome, providing a potential path to more efficient nanocarriers for chemotherapeutic agents by chemical modulation and, giving insights into the rational design of reduction responsive platinum delivery system.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）