BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Haoyu Yang,Xin Chen,Siqi Huang,Hongfang Dai,Zuowei Xiao,Jialong Fan,Honggang Zhang,Ke Du,Yan Qin
Ferroptosis and cuproptosis are two important new forms of ion-dependent cell death, whose processes can be inhibited by high levels of glutathione (GSH) within cells. Therefore, reducing GSH levels is a key strategy for inducing ferroptosis and cuproptosis. Herein, we successfully developed a curcumin (Cur) derivative, bisdemethylcurcumin (bm-Cur), as a novel GSH depletor that simultaneously induces ferroptosis and cuproptosis in hepatocellular carcinoma (HCC). The unique polyphenolic hydroxy structure and double α, β-unsaturated ketone structure of bm-Cur confers its potent GSH scavenging ability, which can effectively deplete GSH by simultaneously inhibiting GSH synthesis and directly consuming GSH levels, ultimately inducing ferroptosis and cuproptosis. Notably, bm-Cur can target mitochondria, induce mitochondrial lipid peroxidation and mitochondrial damage, thereby promoting ferroptosis and cuproptosis-mediated cell death, which demonstrates potential for anti-HCC activity in vitro and in vivo . Moreover, bm-Cur exhibited very low cytotoxicity, excellent biosafety and biocompatibility. In conclusion, this study suggests that bm-Cur may be a novel ferroptosis and cuproptosis activator with significant development potential for further application.
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PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Fangrong Tan,Yuandong Zeng,Donghua Dong,Yan Deng,Zhe Tang,LinGe Wang,Qianqian Yu
Cuproptosis offers a promising alternative to apoptosis-based cancer therapies but faces challenges, such as poor tumor drug accumulation, rapid clearance of copper ionophores, and high intracellular glutathione (GSH). Herein, we developed a GSH-responsive prodrug polymersome (PED@ICG) for copper-independent cuproptosis and synergistic photothermal therapy. Diethyldithiocarbamate (DTC) was covalently attached via disulfide bonds, ensuring a GSH-triggered release and intracellular GSH depletion. The amphiphilic polyprodrug formed stable polymersomes, and ICG coloading endowed imaging ability and NIR-activated photothermal heating. PED@ICG exhibited efficient cellular uptake through dynamin-mediated endocytosis, achieved deep tumor penetration, and selectively released DTC within the reductive tumor microenvironment. In vitro and in vivo studies demonstrated potent anticancer efficacy without the need for exogenous copper, while NIR irradiation further enhanced therapeutic outcomes through localized hyperthermia. This work offers a promising strategy for precise cuproptosis modulation and photothermal synergism, providing a clinically translatable nanoplatform for copper-independent tumor therapy.
研究领域:
纳米医学
·
癌症治疗
·
药物递送
·
光热治疗
·
细胞死亡机制
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.6
Shuang Liu,Xingyu Chen,Xiaojin Liu,Hao Zhang,Keyue Zhou,Yuting Shan,Minghui Chen,Dan Wang,Guohui Cheng
In tumor phototherapy, the intracellular antioxidant defenses, such as high concentrations of glutathione (GSH) and inefficient generation of reactive oxygen species (ROS) significantly restrict the therapeutic efficacy. In this research, we construct a dual-modal GSH depletion and near-infrared (NIR)-triggered nanoplatform (Ce6@CDP) for cascade-amplified photothermal therapy (PTT) and photodynamic therapy (PDT). This nanoplatform featured a hollow mesoporous copper sulfide (CuS) core loaded with Ce6 and encapsulated by a disulfide bond-containing polymer (DS-ANPA-PEG). Upon tumor accumulation, the polymer DS-ANPA-PEG reacts with intracellular GSH to form highly reactive quinone methides (QMs), enabling rapid GSH depletion through alkylation. This dual GSH depletion intensifies oxidative stress, potentiating Ce6-based PDT efficacy. Additionally, the CuS carrier exhibits high photothermal conversion performance (η = 39.68 %), enabling PTT under 808 nm laser irradiation for synergistic tumor eradication. Both in vitro and in vivo studies demonstrate that the PDT/PTT combination therapy significantly inhibits tumor growth while maintaining negligible systemic toxicity. Our findings provide a rational design strategy for developing tumor-microenvironment-responsive multimodal nanoplatforms.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Dandan Liao,Yan Yang,Shuxin Xiong,Jizhou Feng,Cheng Zou,Haibo Peng,Xiaohong Yang,Shao-lin Zhang,Zhi-Peng Wang,Yun He,Chao Huang.
Honokiol (HK), a key bioactive compound extracted from the root and stem bark of Magnolia officinalis , has been a staple in traditional Chinese medicine for over a millennium. Despite its long history of use, HK exhibits low oral bioavailability, which hinders its potential for clinical applications. Herein, we report a GSH-responsive and biodegradable polyphosphazene based Nano-HK particles synthesized via covalent bonding of HK, a disulfide-containing linker, and hexachlorocyclotriphosphazene (HCCP). The Nano-HK particles are uniformly distributed, with an average size of approximately 160 nm. Thanks to the covalent bonding between HK molecules, Nano-HK remains stable in plasma, gradually releasing HK at the tumor site through the reduction of disulfide bonds by the high glutathione (GSH) concentration in cancer cells. This targeted release results in a significantly enhanced inhibitory effect on tumor growth in an A375 xenograft model, outperforming free HK. The results showed no toxic symptoms in mouse or any pathological alterations in major organs. These studies demonstrated that Nano-HK substantially enhanced cytotoxicity against tumor cells compared to free HK, inducing G2/M cell cycle arrest and apoptosis in A375 cells. The conjugated HCCP Nano-HK exhibited both efficacy and safety in mouse, showing promise for further development as a potential treatment for tumors.
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高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Hao Liao,Yuyue Xiong,Jinghang Li,Dongdong Wang,Jinglong Yang,Dong Xie,Lesan Yan
Sonodynamic therapy (SDT) emerges as a promising noninvasive modality for deep tumors but is hindered by the hypoxic tumor microenvironment and glutathione (GSH)-mediated reactive oxygen species (ROS) scavenging. Herein, we report a GSH-responsive nanoplatform fabricated from an mPEG-b-PMNC copolymer, enabling spatiotemporal codelivery of nitric oxide (NO) donors and the sonosensitizer chlorin e6 (Ce6) via self-assembled micelles. Upon exposure to elevated intracellular GSH, the micelles disintegrate to release NO and Ce6 selectively. The released NO attenuates hypoxia through downregulation of hypoxia-inducible factor-1α (HIF-1α) and synergizes with ultrasound-triggered Ce6-generated ROS to yield highly cytotoxic peroxynitrite (ONOO–). This integrated synergy substantially potentiates SDT outcomes, as evidenced by an IC50 of 1.935 μg/mL for mPEG-b-PMNC@Ce6 micelles under ultrasound, outperforming free Ce6 (4.808 μg/mL) and control mPEG-b-PCL@Ce6 (2.736 μg/mL). This polycarbonate-based strategy provides a novel approach for synergistic gas-sonosensitizer delivery, overcoming key limitations of conventional SDT for treating hypoxic tumors.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Huang Shengnan,Xu Zhiling,Zhi Weiwei,Li Yijing,Hu Yurong,Zhao Fengqin,Zhu Xiali,Miao Mingsan,Jia Yongyan
Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.
研究领域:
肿瘤学
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纳米技术
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药学
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生物医学工程
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高影响因子
SENSORS
·
2024
·Vol. 25
·期 1
·34
·
IF 3.4
Yalun Dong,Liyue Wang,Wenfang Liang,Jiqin Zhu,Lu Sun,Long Yi
Glutathione (GSH) plays a crucial role in various physiological processes and its imbalances are closely related to various pathological conditions. Probes for detection and imaging of GSH are not only useful for understanding GSH chemical biology but are also important for exploring potential theranostic agents. Herein, we report a fast intramolecular thiol-activated arylselenoamides (FITA)-based fluorescent probe using 2,4-dinitrophenyl alkylthioether as a sulfydryl-selective receptor for the first time. The fluorescence of the probe was low due to the double effects of PET, while the probe exhibits an 86-fold fluorescence enhancement at 460 nm after GSH activation and a detection limit of 0.95 μM. Furthermore, the probe is low-toxic and capable of imaging cellular GSH. This work further expands the design and applicability of theFITA-based platform, offering a new thiol-deprotection strategy for development of fluorescent probes.
研究领域:
生物化学
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医学诊断
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化学生物学
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高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Sheng Xu,Ziwei Hu,Weihao Zheng,Chaozhen Qin,Xiaoyu Bai,Qinghua Yang,Tao Zeng,Dandan Mo,Bo Zhou,Chun Lu,Xiaomin Chen,Biying Tan,Jinmin Zhao,Li Zheng
Osteosarcoma (OS), a highly malignant primary tumor, poses significant threats. Chemotherapy remains the main treatment approach but is limited by low drug bioavailability, poor permeability, and notable side effects. Herein, a near-infrared light (NIR)-driven and GSH-responsive poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP) nanomotor, wherein disulfide bonds served as GSH sponsors and platinum nanoparticles as producers of reactive oxygen species (ROS) to induce cell apoptosis, combined with NIR-driven propulsion to enhance the inhibitory effect of encapsulated doxorubicin (DOX). The results demonstrated that the PSPDP nanomotor can be effectively driven due to its good photothermal properties, with its movement speed increased 2.10 times under NIR laser exposure. Additionally, the efficiency of DOX release increased with the increase in GSH concentration, demonstrating favorable GSH responsiveness. Pt-NPs also exhibited good photothermal properties, enabling self-thermophoresis to drive. Minimal cytotoxic effects of PSPDP were observed on a series of cell lines compared with DOX solution and Pt-NPs. Notably, the Pt-NPs generated a significant amount of ROS, synergistically enhancing the therapeutic effect of DOX, as evidenced by a 5.53-fold increase in OS cell growth inhibition and evident osteosarcoma growth inhibition in the nude mice model. Thus, the NIR-driven, localized, and low-toxic nanomotor may offer a promising therapeutic strategy for OS intervention. Statement of significance Enhancing drug penetration efficiency and developing delivery systems that respond to the tumor microenvironment to release drugs are effective strategies for treating osteosarcoma (OS). Here, a near-infrared (NIR) light-driven and glutathione (GSH)-responsive nanomotor, integrating poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP), was produced and used for OS treatment. This PSPDP nanomotor exhibits significant advancements in photothermal activation and self-thermophoresis, enabling a 2.10-fold increase in movement speed under NIR exposure. Such enhanced motility improves the localized delivery and controlled release of doxorubicin, thus increasing drug bioavailability and minimizing systemic toxicity. Additionally, the nanomotor's ability to generate reactive oxygen species significantly amplifies its therapeutic impact, evidenced by a remarkable 5.53-fold increase in tumor growth inhibition. These features make the PSPDP nanomotor a promising candidate for effective and targeted OS treatment strategies.
研究领域:
肿瘤学
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纳米医学
·
生物材料学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaohong Zhu,Tiantian Feng,Yidan Chen,Yao Xiao,Wei Wen,Xiuhua Zhang,Dong Wang,Shengfu Wang,Jichao Liang,Huayu Xiong
Skin wound healing, particularly diabetic wound healing, is a common clinical challenge. Reducing bacterial infection and promoting angiogenesis are key strategies for diabetic wound healing. In this study, we construct the porphyrin-based Cu-covalent organic frameworks (Cu-COF) through a Schiff base condensation reaction, and then functionalize Cu-COF with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-DSPE), denoted as PEG/Cu-COF, for enhancing diabetic wound healing. PEG/Cu-COF exhibits dual enzymatic properties (glutathione (GSH) oxidase-like and peroxidase (POD)-like nanozymes), facilitating the depletion of GSH and the generation of reactive oxygen species (ROS) through a self-cascading enzymatic reaction, thereby leading to chemodynamic therapy (CDT). Density functional theory (DFT) calculations are employed to investigate the catalytic mechanism and the results reveal that Cu-COF exhibits higher catalytic activity for POD. Moreover, porphyrin-based COF generates singlet oxygen and localize heating under white light and near-infrared irradiation, respectively. Both in vitro and in vivo experiments demonstrate that PEG/Cu-COF exhibits multimodal synergistic sterilization and promotes angiogenesis, collagen deposition, and re-epithelialization during diabetic wound healing. This work highlights the potential utilization of PEG/Cu-COF for self-supplying hydrogen peroxide (H 2 O 2 ) and amplifying self-cascade reactions to address the limitations of enzymatic treatment, while the synergistic effect of phototherapy improves sterilization and minimizes side effects in vivo .
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
药学
·
伤口愈合
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高影响因子
JOURNAL OF LUMINESCENCE
·
2012
·
IF 2.102
Zhengqing Liu,Pengfei Yin,Huiping Gong,Pingping Li,Xiaodan Wang,Youqiu He
Aqueous glutathione (GSH)-capped CdTe / ZnS QDs with the diameter of 3–4 nm were synthesized. The fluorescence of CdTe / ZnS QDs at 577 nm was quenched in the presence of rifampicin (Rfp), with excitation wavelength at 350 nm. The mechanism of the interaction of CdTe / ZnS QDs with Rfp was investigated. Under the optimal conditions, the calibration plot of ln( F 0 /F ) was linear in the range 0.83–56 μg mL −1 with concentration of Rfp, and the detection limit was 0.25 μg mL −1 . The proposed method was successfully applied to the determination of Rfp in its commercial capsules, and satisfactory results were obtained. The recovery of the method was in the range 98.6–103.2%.
研究领域:
分析化学
·
药学
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DOI
高影响因子
ANALYST
·
2020
·Vol. 145
·期 21
·7063-7070
·
IF 3.978
Zhiying Li,Yadan Xue,Wenhua Zhao,Daixin Ye
Glutathione (GSH) plays an important role in the biochemical defense system of the human body. Designing an exceptional probe to detect trace amounts of GSH is of great significance for studying the oxidative stress reaction and related diseases. In this study, a selective and sensitive orange-red emitting copper nanocluster(CuNC)-based fluorescent probe for the detection of GSH was devised in the matrix of polyvinylpyrrolidone (PVP) using hydrazine hydrate (HYD) as the reducing agent and 2-mercaptobenzothiazole (MBT) as the stabilizer. A peaceable without external assistance method (room temperature reaction) was employed to synthesize fluorescent CuNCs with orange-red luminescence emission at 606 nm upon excitation at 377 nm. The fluorescence intensity of CuNCs was found to decrease or even quench by the addition of GSH, which indicated the stronger binding ability of –SH in GSH with the CuNCs losing the protection of PVP. Based on this principle, the present sensor system exhibits a good linear response towards GSH ranging from 0.10 to 40 μM, and the limit of detection was found to be 12.4 nM. Moreover, due to the excellent selectivity and high sensitivity of the GSH sensor, it might act as a potential probe for the detection of GSH in the lysosomal environment of tumor cells. Thus, this strategy has a promising application potential for the early identification and prevention of cancer with low toxicity and good stability.
研究领域:
生物化学
·
医学诊断
·
材料科学
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高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Ling-jun Zhu,Lian-shuai Gu,Tian-yi Shi,Xiang-yang Zhang,Bai-Wang Sun
Cisplatin is a highly effective antitumor drug, which can kill cancer cells by crossing-linking DNA and inhibiting transcription, but this process is limited by the combination of cisplatin and many endogenous nucleophiles, such as glutathione (GSH). Thus, when cisplatin enter cells, it is potentially vulnerable to cytoplasmic inactivation by GSH. To settle this bottleneck, we designed and synthesized a probe compound (Probe 1) and fabricated pH-responsed cisplatin, Probe 1-loaded lipid-polymer hybrid NanoParticles (CPNPs) using a single-step sonication method. Probe 1 can specifically bind to GSH, thus avoiding the combination of GSH and cisplatin, and enhancing the pharmacological activity of cisplatin. In vitro studies have suggested CPNPs, compared with cisplatin, loaded lipid-polymer hybrid NanoParticles CNPs (Not contain Probe 1), could efficiently kill MCF-7 human breast cancer cells and A549 human nonsmall lung cancer cell. Hence, the CPNPs provided a new idea for treating cancer.
研究领域:
药理学
·
肿瘤学
·
纳米医学
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PubMed
高影响因子
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