DALTON TRANSACTIONS
·
2024
·
IF 3.5
Linming Li,Yan Chen,Ming Zhang,Suying Li,Shuaiqi Feng,Yan-Qin He,Ning Zhang,Zhifang Liu,Meifeng Liu,Qing-Peng Wang
Protective autophagy is a promising target for antitumor drugs exploration. A hydroxychloroquine (HCQ) platinum(IV) complex with autophagy suppressing potency was developed, which displayed potent antitumor activities with a TGI of 44.2% against 4T1 tumors in vivo and possessed rather lower toxicity than cisplatin. Notably, it exhibited satisfactory antimetastatic activities toward lung pulmonary metastasis models with inhibition rate of 49.6%, which was obviously more potent than CDDP (21.6%). Mechanism detection revealed that it caused serious DNA damage and upregulated the expression of γ-H2AX and p53. More importantly, the incorporation of autophagy inhibitor HCQ endowed platinum(IV) complex with potent autophagy impairing properties by perturbing lysosomal function in tumor cells, which promoted apoptosis synergistically with the DNA injury. Then, the impaired autophagy further led to the suppression of hypoxia and inflammation in tumor microenvironment by downregulating ERK1/2, HIF-1α, iNOS, caspase1 and COX-2. Adaptive immune response was improved by inhibiting immune checkpoint PD-L1, and further increasing CD4+ and CD8+ T cells in tumors. Then, tumor metastasis was effectively inhibited by restraining angiogenesis through inhibiting VEGFA, MMP-9, and CD34.
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BIOMATERIALS
·
2025
·
IF 12.9
Yu Wang,Hongrui Fan,Qinjun Chen,Haolin Song,Xuwen Li,Boyu Su,Tao Sun,Leilei Cheng,Chen Jiang
Metabolic reprogramming in pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge to the efficacy of gemcitabine-based chemotherapy. Aberrant activation of intracellular pyrimidine metabolism is a key factor contributing to the reduced effectiveness of gemcitabine. Combining gemcitabine with metabolic regulators targeting critical pathways may alleviate gemcitabine resistance. In this study, we focus on the abnormal activation of dihydroorotate dehydrogenase (DHODH) in PDAC cells, a pivotal enzyme in the de novo pyrimidine synthesis pathway that diminishes cellular sensitivity to gemcitabine and catalyzes the reduction of ubiquinone to ubiquinol, playing an essential role in maintaining cellular redox homeostasis. To address these challenges, we developed GE11 peptide-modified polyphenol-iron chelate nanoparticles for co-delivery the long carbon chain-modified gemcitabine and the DHODH inhibitor leflunomide, with peptide modification enabling nanoparticles to target PDAC cells with high expression of epidermal growth factor receptor. The nanoparticles demonstrated the ability to induce mitocytosis and achieve deep tumor penetration in PDAC tissues. Upon drug release at the core lesion, the three components, modified gemcitabine, leflunomide and iron ions synergistically enhanced tumor cell killing by alleviating gemcitabine resistance and disrupting cellular redox homeostasis to induce multimodal cell death. In an in situ pancreatic cancer mouse model, this strategy exhibited superior anti-tumor efficacy compared to the standard AG chemotherapy regimen (nab-paclitaxel and gemcitabine), even at a 6.3-fold lower gemcitabine concentration. These findings underscore the potential of this approach as a highly effective therapeutic strategy for PDAC treatment.
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高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2025
·Vol. 48
·期 7
·e70226
·
IF 2.8
Kejie Wang,Bingye Shi,Yihui Chen,Chunyan Hou,Xie Li,Xiaoqiang Qiao,Tingting Wang
Quinine, chloroquine, and hydroxychloroquine are effective antimalarial drugs that have shown antiviral activity against SARS-CoV-2 in initial in vitro studies. However, their excessive use can lead to adverse effects in humans. Therefore, rapid and accurate analysis of these inhibitors in whole blood samples is crucial for public health, although this presents significant challenges. In this study, perfluorooctyl-functionalized halloysite nanotubes were synthesized and used as sorbents for dispersive solid-phase extraction. The developed sorbents interacted with inhibitors through various mechanisms, including hydrophobic interactions, electrostatic interactions, F–π interactions, and hydrogen bonding. Notably, their adsorption capacity was twice that of unmodified halloysite nanotubes. By combining the perfluorooctyl-functionalized halloysite nanotubes-based dispersive solid-phase extraction method with liquid chromatography-tandem mass spectrometry, an analytical method was developed to determine concentrations of the three inhibitors in whole blood samples. Under optimized conditions, the limits of detection ranged from 1.2 to 2.1 ng/mL. The recoveries achieved 91.9%–101.5% for intra-day and 92.8%–101.2% for inter-day. The inter- and intra-day relative standard deviations were in the range of 0.6%–3.8% and 2.3%–8.1%, respectively. This study introduces a novel approach for developing sorbents to target drugs and presents an innovative analytical method for therapeutic monitoring. These advancements will facilitate the evaluation of the pharmacokinetics of these inhibitors in patients and support ongoing clinical trials.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·
IF 12.6
Xu Lian,Chen Jiangwei,Zhang Wenli,Du Qianying,Huang Xin,Luo Ying,Wang Yi,Chen Sijin,Rong Xiyue,Liu Jia,Xu Zhongsheng,Ran Haitao,Liu Yun,Guo Dajing,Xu Jie
Deep vein thrombosis (DVT) is a serious medical condition that can lead to life-threatening complications. Conventional or nanotechnology-based antithrombotic therapies frequently lead to incomplete thrombolysis and may result in DVT recurrence. Emerging evidence highlights that the persistent neutrophil extracellular traps (NETs) scaffold synergistically interacts with reactive oxygen species overproduction and inflammatory cascades, collectively compromising thrombus resolution and establishing a prothrombotic microenvironment for recanalization failure. Hence, in response to this pathomechanism, a bismuth (Bi)-based nanoplatform (PSA@Bi-TNK-HCQ; PBTH) was constructed. PBTH nanoparticles (NPs) were delivered in a targeted manner to activated endothelial cells via polysialic acid (PSA) and enabled thrombus visualization through dual-energy computed tomography imaging. Therapeutically, a dual-drug antithrombotic effect was achieved through the breakdown of fibrin by tenecteplase (TNK) and the inhibition of NET structures by hydroxychloroquine (HCQ). This mechanistically complementary approach showed superior thrombolytic performance in vivo compared to monotherapy, with a residual thrombus rate of 18.7%. Furthermore, the multienzyme-like activities of PBTH NPs restored endothelial function by mitigating oxidative stress damage and inflammation, thereby preventing thrombus recurrence and pulmonary embolism. The vicious cycle of NET-mediated thrombosis-associated immune dysregulation, a locally abnormal thrombotic microenvironment, and endothelial dysfunction was ultimately broken. This work provides a promising two-pronged approach to the treatment of DVT by increasing the effectiveness of thrombolysis while reducing the risk of reocclusion. Graphical
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高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 6
·1-11
·
IF 5.3
Chen Yun-Ting,Han Jing-Wen,Yu Zi-Wei,Yang Ruo-Yu,Wu Mei-Juan,Huang Pin-Fang,Liu Meng-Meng
A decentralized electrochemical immunosensor was developed using a smartphone and a portable electrochemical workstation. The system employs a gold nanoflower-modified screen-printed carbon electrode (AuNFs/SPCE) for the sensitive measurement of adalimumab (ADL) in human serum via antigen‒antibody recognition. Scanning electron microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy were used to investigate the AuNFs/SPCE. Compared with the bare SPCE, the AuNFs/SPCE has a 1.47-fold larger specific surface area, which enhances the capture efficiency of ADL for signal amplification. Electrode modification and antigen‒antibody assembly processes are characterized by cyclic voltammetry and electrochemical impedance spectroscopy. The immunosensor achieves excellent electrochemical properties by optimizing experimental conditions, which improves the signal-to-noise ratio and thus the analytical performance. Under the best experimental conditions, the immunosensor has a quantitative range of 0.05‒4 μg/mL in diluted human serum with a detection limit of 9.1 ng/mL, which is consistent with the effective therapeutic window of ADL in clinical settings. The prepared electrodes maintain 10-day stability, while with high reproducibility at different ADL concentrations. High recoveries in the range 94.08‒108.6% are obtained in human serum samples. Furthermore, ADL in the serum samples was measured by both ELISA and the developed sensor. Pearson and Bland‒Altman analyses revealed a consistent trend between the two methods. Therefore, this immunosensor is a promising tool for the point-of-care (POC) measurement of ADL in clinical samples, providing valuable insights for personalizing ADL dosing regimens in clinical practice. Graphical
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