BIOMATERIALS
·
2025
·
IF 12.9
Xinghua Yu,Lingan Zeng,Haiyan Chen,Xuemei Dong,Fan Wen,Mingming Wang,Runqi Pan,Yujun Zhang,Wei Zhu,Dingyuan Yan,Dong Wang,Fei Sun
Asthenozoospermia, a leading cause of male infertility characterized by impaired sperm motility, poses significant therapeutic challenges due to the restrictive blood-testis barrier (BTB). To address this limitation, we engineered multifunctional extracellular vesicles (EVs) derived from umbilical cord mesenchymal stem cells, loaded with adenosine triphosphate (ATP) to synergistically restore cellular bioenergetics and suppress ferroptosis. These EVs were further functionalized with an aggregation-induced emission luminogen for near-infrared-II (NIR-II) fluorescence imaging, enabling real-time visualization of their efficient BTB penetration and targeted accumulation within testicular tissues. Upon localization in the seminiferous tubules, the released ATP directly replenishes the energy reserves of spermatogenic cells and enhances sperm motility in asthenozoospermia models. Simultaneously, the EVs upregulate glutathione peroxidase 4, mitigating ferroptosis and synergizing with ATP to restore metabolic homeostasis. In vivo studies demonstrate the dual efficacy of this platform: the EVs precisely traverse the BTB while robustly inhibiting ferroptosis without systemic toxicity, significantly improving sperm count and kinematic parameters (motility, velocity). This study presents a multifunctional nanoplatform that integrates NIR–II–guided imaging, ATP-mediated energy restoration, and pathology-specific ferroptosis inhibition, providing a promising non-invasive therapeutic strategy for asthenozoospermia.
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DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Xiaoliang Qi,Yajing Xiang,Ying Li,Jiajia Wang,Yuxi Chen,Yulong Lan,Jinsong Liu,Jianliang Shen
Adenosine triphosphate (ATP)-activated prodrug approaches demonstrate potential in antibacterial uses. However, their efficacy frequently faces obstacles due to uncontrolled premature activation and spatiotemporal distribution differences under physiological circumstances. Herein, we present an endogenous ATP-activated prodrug system (termed ISD3) consisting of nanoparticles (indole-3-acetic acid/zeolitic imidazolate framework-8@polydopamine@platinum, IZPP) embedded in a silk fibroin-based hydrogel, aimed at treating multidrug-resistant (MDR) bacteria-infected pressure ulcers. Initially, an ultraviolet-triggered adhesive ISD3 barrier is formed over the pressure ulcer wound by a simple local injection. Subsequently, the bacteria-secreted ATP prompts the degradation of IZPP, allowing the loaded IAA prodrug and nanozyme to encounter spatiotemporally on a single carrier, thereby efficiently generating reactive oxygen species (ROS). Exposure to 808 nm near-infrared light enhances the catalytic reaction speed, boosting ROS levels for stronger antibacterial action. Once optimal antibacterial action is reached, ISD3 switches to a dormant state, halting any further ROS production. Moreover, the bioactive components in ISD3 can exert anti-inflammatory functions, aiding in pressure ulcer recovery. Overall, our research introduces a hydrogel prodrug strategy activated by bacterial endogenous ATP, which precisely manages ROS generation and accelerates the recovery of MDR bacteria-infected pressure ulcers.
研究领域:
生物医学工程
·
微生物学
·
药剂学
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Min Gao,Yue Song,Jing Liang,Tiantian Chen,Jiajia Luo,Panyu Du,Han Wang,Hongyu Leng,Zheng Wang,Xinlong Ma,Kai Wang,Yanjun Zhao
Concurrent induction of apoptosis and ferroptosis is promising in handling heterogenous cancers. We report a tailored polymeric micellar nanoplatform for the combinational anti-tumor therapy. Two stimuli-responsive amphiphlic block copolymers were synthesized, bearing three functional moieties, i.e. azobenzene, nitroimidazole and 3-fluorophenylboronic acid. Azobenzene could enhance the cellular uptake of micelles. Nitroimidazole and 3-fluorophenylboronic acid could deplete the reduced nicotinamide adenine dinucleotide phosphate (NADPH), glucose and adenosine triphosphate (ATP) under hypoxia, sensitizing ferroptotic and apoptotic cell death. The proof-of-concept was demonstrated in a triple-negative breast cancer cell line (MDA-MB-231). Irrespective of the free or encapsulated form, doxorubicin and auranofin showed a synergistic action, evidenced by a low combination index (< 1). The co-delivery micelles showed improved potency than the single drug-loaded micelles in terms of the biomarkers of apoptosis ( e.g. caspase 3/9, cytochrome c and ATP) and ferroptosis ( e.g. thioredoxin reductase, thioredoxin, glutathione, NADPH, malondialdehyde and lipid peroxides). The apoptosis and ferroptosis induction ability of cargo-free micelles was proved. The in vivo efficacy was verified in the MDA-MB 231 tumor-bearing nude mice model. The current work offers a promising strategy of combinational anti-tumor drug delivery for potent induction of ferroptosis and apoptosis via the sensitization effect of vehicle in the hypoxic tumor.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2018
·
IF 5.738
Zhanwei Zhou,Minghua Zhang,Yadong Liu,Chenzi Li,Qingyan Zhang,David Oupicky,Minjie Sun
Cationic polyplex as commonly used nucleic acid carriers faced several shortcomings, such as high cytotoxicity, low serum stability, and slow cargo release at the target site. The traditional solution is covering a negative charged layer (e.g., hyaluronic acid, HA) via electrostatic interaction. However, it was far from satisfactory for the deshielding by physiological anions in circulation (e.g., serum proteins, phosphate). In this study, we proposed a new strategy of reversible covalent cross-linking to enhance stability in circulation and enable stimuli-disassembly of polyplexes in tumor cells. Here, 25k polyethylenimine (PEI) was chosen as model polycations for veriying the hypothesis. HA-PEI conjugation was formed by the cross-linking of adenosine triphosphate grafted HA (HA-ATP) with phenylboronic acid grafted PEI (PEI–PBA) via the chemical reaction between PBA and ATP. Compared with noncovalent polyplex by electrostatic interaction (HA/PEI), HA-PEI exhibited much better colloidal stability and serum stability. The covered HA-ATP layer on PEI–PBA could maintain stable in the absence of physiological anions, while HA layer on PEI in HA/PEI group showed obvious detachment after anion’s competition. More importantly, the covalent cross-linking polyplex could selectively release siRNA in the ATP rich environment of cytosol and significantly improve siRNA silence. Besides, the covalent cross-linking with HA-ATP could effectively reduce the cytotoxicity of cationic polyplex, improve the uptake by B61F10 cells and promote the endosomal escape. Consequently, this strategy of HA-PEI conjugation significantly enhanced the siRNA transfection in the absence or presence of FBS (fetal bovine serum) on B16F10 cells and CHO cells. Taken together, the reversible covalent cross-linking approach shows obvious superiority compared with the noncovalent absorption strategy. It held great potential to be developed to polish up the performance of cationic polyplex on reducing the toxicity, enhancing the serum tolerance and achieving controlled release of siRNA at target site.
研究领域:
药学
·
生物技术
·
纳米医学
·
分子生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Min Jiang,Xiaoxue Xi,Zhen Wu,Xiuhua Zhang,Shengfu Wang,Wei Wen
In situ and quantitative measurements of adenosine 5′-triphosphate (ATP) in single living cells are highly desired for understanding several sorts of necessary physiological and pathological processes. Due to its small size and high sensitivity, an ultra-microelectrode can be used for single-cell analysis. However, ATP is difficult to detect in single cells because it is nonelectroactive and low in content. Herein, we introduced an electrochemical nano-biosensor based on an amphiphilic aptamer-assisted carbon fiber nanoelectrode (aptCFNE) with high signal-to-noise ratio. The low current (e.g., 60 pA) and the tiny diameter of the tip (ca. 400 nm) of the nanosensor made it noninvasive to living cells. The amphiphilic aptamer has good biocompatibility and can be stably modified to the surface of functionalized electrodes. CFNE, which was modified with ferrocene-labeled aptamer, could quickly and selectively detect ATP content in the nucleus, cytoplasm, and extracellular space of single HeLa cells. The results showed that the ATP contents in the nucleus, cytoplasm, and extracellular space were 568 ± 9, 461 ± 20, and 312 ± 4 μM, respectively. The anticancer drug treatment effects on the cellular level were further recorded, which was of great significance for understanding ATP-related biological processes and drug screenings. This strategy is universally applicable to detect other targets by changing the aptamer sequence, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level.
研究领域:
分析化学
·
生物化学
·
生物医学工程
·
药理学
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DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2026
·
IF 3.9
Wenlong Xing,Yin Zhu,Jiahao Wu,Shijia Li,Zhenyu Zhao,Jinsong Zhang,Shaowei Bo,Ji Zeng,Jiangling Peng
The rapid and accurate detection of adenosine 5′-triphosphate (ATP) is crucial for clinical diagnostics, bioanalysis, and food safety. This study presents two novel aggregation-induced emission (AIE)-active probes, BIP-PP-1 and BIP-PP-2 , derived from a new N-heterocyclic AIEgen core, benzo[4,5]imidazo[1,2- c ]pyrimidine (BIP). The optimized probe, BIP-PP-2 , functions as a high-performance ATP sensor with a large Stokes shift, high sensitivity (LOD = 0.85 μM, linear range 0 – 90 μM), and excellent selectivity over structurally similar anions such as ADP, AMP, CTP, TTP, and UTP, a feature seldom achieved in small-molecule ATP probes. This unique selectivity is attributed to the novel BIP core, where specific π-π stacking and hydrogen-bonding interactions with the adenine moiety of ATP provide a superior stereoelectronic match, driving precise recognition and AIE-based fluorescence enhancement via a synergistic combination of electrostatic and non-covalent forces. BIP-PP-2 was successfully applied in real-time ATP imaging within live bacterial cells and, notably, in the rapid visual detection of bacterial contamination in beverages using a portable 365 nm UV lamp, achieving a visual detection limit of 3.9 × 10 5 CFU mL −1 under ambient light. This work introduces the BIP scaffold as a promising platform for functional dye design and establishes BIP-PP-2 as a robust analytical tool for on-site bioanalysis and food safety monitoring. © 2001 Elsevier Science. All rights reserved.
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DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2019
·
IF 3.206
Wen Nie,Fangfang Wang,Runqing Hao,Lu Zhang,Qian Chen,Fanmei Wei,Xiaotong Li,Robert Loffredo,Zhenbo Liu,Yongming Liu
For aqueous two-phase extraction (ATPE), adsorbents such as primary secondary amine (PSA) are usually used to remove fat and protein in meat samples. However, it was determined that PSA adsorbed approximately 5% of measured sulfonamides (SAs), which is the reason for the low recovery rate. To overcome this adverse PSA effect, a solid phase extraction (SPE) method was used for purification and enrichment after the formation of aqueous two-phase. Based on these, A new aqueous two-phase sample pretreatment method with solid phase extraction (ATP-SPE) to detect sulfonamides in fish meat is proposed. Fluorescence quenching showed that for 6 SAs, hydrogen bonding and van der Waals force played the major role in the binding reaction with fish serum albumin protein. In addition, in the 80% ACN aqueous solution, a slow protein denaturation took place and the drugs bound with the protein were released, which is more conducive to the aqueous two-phase extraction. In order to obtain better separation effect, the factors for synthesis of hydrophobic-lyophobic balance (HLB) packing for SPE were explored. Stirring speed is the most important factor affecting the particle size of microspheres . After purification and enrichment by SPE, samples were directly analyzed by HPLC. The analytical process was validated in the fish sample matrix by the analysis of spiked blank samples. The mean recoveries of this method were 80.1–95.1% with RSD values of 1.37–3.95%. The detection limits were 5.8–11.7 ng/g. The new ATP-SPE pretreatment method provides a new way for better recovery of veterinary drugs in meat products.
研究领域:
分析化学
·
食品科学
·
药理学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Zhezhu Nan,Hengyu Liu,Linrong Shi,Hongrui Zhu,Junjie Chen,Tali Ilovitsh,Daocheng Wu,Mingxi Wan,Yi Feng
Focused ultrasound, as a protocol of cancer therapy, might induce extracellular adenosine triphosphate (ATP) release, which could enhance cancer immunotherapy and be monitored as a therapeutic marker. To achieve an ATP-detecting probe resistant to ultrasound irradiation, we constructed a Cu/N-doped carbon nanosphere (CNS), which has two fluorescence (FL) emissions at 438 and 578 nm to detect ultrasound-regulated ATP release. The addition of ATP to Cu/N-doped CNS was conducted to recover the FL intensity at 438 nm, where ATP enhanced the FL intensity probably via intramolecular charge transfer (ICT) primarily and hydrogen-bond-induced emission (HBIE) secondarily. The ratiometric probe was sensitive to detect micro ATP (0.2–0.6 μM) with the limit of detection (LOD) of 0.068 μM. The detection of ultrasound-regulated ATP release by Cu,N-CNS/RhB showed that ATP release was enhanced by the long-pulsed ultrasound irradiation at 1.1 MHz (+37%, p < 0.01) and reduced by the short-pulsed ultrasound irradiation at 5 MHz (−78%, p < 0.001). Moreover, no significant difference in ATP release was detected between the control group and the dual-frequency ultrasound irradiation group (+4%). It is consistent with the results of ATP detection by the ATP-kit. Besides, all-ATP detection was developed to prove that the CNS had ultrasound-resistant properties, which means it could bear the irradiation of focused ultrasound in different patterns and detect all-ATP in real time. In the study, the ultrasound-resistant probe has the advantages of simple preparation, high specificity, low limit of detection, good biocompatibility, and cell imaging ability. It has great potential to act as a multifunctional ultrasound theranostic agent for simultaneous ultrasound therapy, ATP detection, and monitoring.
研究领域:
生物医学工程
·
分子生物学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Chao Gao,Ye Feng,Suyi Liu,Bin Chen,Miaomiao Ding,Dailing Du,Wenjing Zhang,Daniela A. Wilson,Yingfeng Tu,Fei Peng
Combining artificial cellular compartmentalization and intelligent motion benefits of micro/nanomotors, light is used as energy input to construct an artificial cell-based micromotor capable of photosynthetic anabolism and intelligent directional movement. This system is assembled from phospholipids functionalized with F-ATP synthase and molybdenum disulfide (MoS 2 ) nanoparticles (Vesical@MoS 2 -ATPase). The underlying mechanism involves the generation of protons (H + ) through photo-hydrolysis of MoS 2 nanoparticles within vesicles, which generates a local electroosmotic flow inside the vesicles and drives the negatively charged MoS 2 toward light. The established proton gradient across the phospholipid membrane, in turn, drives the ATP synthase to catalyze ATP production. Both in vitro and in vivo models demonstrate that the micromotor can elevate local intracellular ATP levels upon light and improve the metabolism of denatured chondrocytes. This cell mimicry, with capabilities of migration and biosynthesis, emerges as a promising platform for the next generation of functional bio-interface.
研究领域:
生物医学工程
·
纳米医学
·
再生医学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2018
·
IF 8.173
Li-Ping Jia,Ruo-Nan Zhao,Li-Juan Wang,Rong-Na Ma,Wei Zhang,Lei Shang,Huai-Sheng Wang
The present work reported a simple, lable-free and sensitive electrochemical method for the detection of protein kinase A (PKA) activity. This method was based on the specific recognition of aptamer and the aptamer-induced hybridization chain reaction (HCR) amplification strategy. The aptasensor was constructed by immobilizing capture probe on a gold electrode via an Au–S bond. When adenosine triphosphate (ATP) aptamer was introduced, its one terminus hybridized with capture probe and the other hybridized with the complementary region of an auxiliary probe, which other region triggered HCR between two hairpin DNA (H1 and H2) to form a long DNA concatamer. At last a large number of electroactive methyle blue (MB) molecules were assembled on the dsDNA concatamer, which generated a significantly amplified electrochemical signal. In the presence of ATP, the HCR would not be performed because the aptamer specifically bond to ATP and the electrochemical response would decrease. However, when ATP and PKA coexisted, the electrochemical response would recovery because that ATP had been translated into ADP by PKA. So the activity of PKA could be effectively monitored according to the change of electrochemical signal. Based on the HCR amplification strategy, the aptasensor showed a wide linear range (4 − 4 ×10 5 U L −1 ) and a low detection limit (1.5 U L −1 ) for the detection of PKA. Furthermore, the method was applied to study the inhibitory effect of H-89 on PKA activity. The developed aptasensor was also used to the analysis of drug-induced PKA activity in cell lysates, indicating the potential application of the developed method in the fields of clinical diagnostics and discovery of new targeted drugs.
研究领域:
生物化学
·
医学诊断
·
药物发现
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DOI
PubMed
高影响因子
TOXICOLOGICAL SCIENCES
·
2017
·Vol. 161
·期 2
·431-442
·
IF 4.081
Wang Jia,He Huan,Xiang Chen,Fan Xiao-Yang,Yang Li-Yun,Yuan Lian,Jiang Feng-Lei,Liu Yi
As a novel delocalized lipophilic cation, F16 selectively accumulates in mitochondria of carcinoma cells and shows a broad spectrum of antiproliferative action towards cancer cell lines. In order to reveal the mode of action and molecular mechanism of F16 inducing cytotoxicity, we investigated the effects of F16 on cancer cells and isolated mitochondria relative to its precursor compound (E)-3-(2-(pyridine-4yl)vinyl)-1 H-indole (PVI), which has a similar structure without positive charge. It was found that PVI did not accumulate in mitochondria, and exhibited lower cytotoxicity compared to F16. However, when they were directly incubated with mitochondria, both F16 and PVI were observed to induce damage to mitochondrial structure and function. Moreover, it was found that F16 as well as PVI acted as uncouplers on mitochondria, and further rescue experiments revealed that the addition of adenosine 5′-triphosphate was the most effective way to recover the cell viability decreased by F16. Thus it was concluded that the decreased intracellular adenosine 5′-triphosphate availability induced by the uncoupling effect of F16 was a major factor in F16-mediated cytotoxicity. Futhermore, the results indicated that the uncoupling effect of F16 is attributed to its chemical stucture in common with PVI but independent of its positive charge. The study may shed light on understanding the underlying mechanism of action for F16, and providing suggestions for the design of new mitochondria-targeted antitumor molecules.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2023
·
IF 4.5
Xiang Liu,Bing-Ke Li,Qin-Xue Liu,Peng-Fei Li,Fei Ling,Gao-Xue Wang
Viral nervous necrosis (VNN) caused by nervous necrosis virus (NNV) is a major threat to the global aquaculture industry, resulting in huge economic losses. In this study, we evaluated a naturally anthraquinone, rhein, as a potential therapeutic agent against NNV. Rhein effectively inhibited NNV-induced cytopathic effects (CPE) at a concentration of 18.84 μM, with an inhibitory concentration (IC 50 ) against NNV replication of 8.77 μM. Moreover, the study revealed a possible anti-NNV mechanism. Rhein could disrupt NNV-induced S-phase cell cycle arrest by inhibiting ATP synthesis, and cell cycle arrested in S phase is favorable for NNV replication, which in turn inhibits NNV replication. The therapeutic effect of rhein was also evaluated in vivo , where the survival rate of NNV infected grouper was increased by 26.7% with the treatment of 10 mg/kg rhein. Our findings demonstrated the potential of rhein as a pharmacological compound that exerts significant antiviral activity against NNV by modulating the cell cycle and ATP synthesis. Consequently, rhein has shown significant promise as a medication for the prevention and treatment of viral infections in aquaculture.
研究领域:
水产养殖
·
病毒学
·
药理学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）