BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
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2018
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IF 3.438
Wendiao Zhang,Ye Xu,Guo Chen,Kun Wang,Wenzhe Shan,Yong Chen
The composition, structure, production, motion, fate, and functions of cell-bound membrane vesicles pre-existing in the plasma membrane of cells are poorly understood. Here, single-vesicle tracking of individual cell-bound membrane vesicles in the plasma membrane of endothelial cells treated with or without various reagents was performed to investigate the motion of cell-bound membrane vesicles. The efficacy of each of these reagents was confirmed prior to single-vesicle tracking. Via single-vesicle tracking, we found that oxLDL, TNF-α, and VEGFα significantly increased the average number of cell-bound membrane vesicles per cell, implying that cell activation by oxLDL, TNF-α, and VEGFα could trigger the production of cell-bound membrane vesicles. It was also found that oxLDL, TNF-α, VEGFα, LPS, and MβCD but not LDL could significantly affect the motion speed of cell-bound membrane whereas none of them could significantly influence the displacement (moving range) of cell-bound membrane vesicles. The single-vesicle tracking further revealed that the average number of cell-bound membrane vesicles per cell and the mean speed/displacement of individual cell-bound membrane vesicles could be dramatically altered by the cytoskeleton-disrupting reagents (cytochalasin D and nocodazole). The data imply that the production and movement of cell-bound membrane vesicles are probably controlled by intracellular cytoskeletons and capable of being affected by multiple conditions e.g. cell activation, membrane fluidity alteration, and others.
研究领域:
细胞生物学
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生物物理学
·
药理学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Mengxin Zhang,Yingyu Zhang,Xianwei Zhang,Qionglin Wang,Kangbo Liu,Muchun Yu,Lifeng Li,Zhidan Yu,Huan Zhao,Weyland Cheng,Wancun Zhang
Specific imaging of tumor cells with high sensitivity is urgently needed for evaluating the risk of tumor metastasis and progression. However, traditional tumor cell imaging strategies are still restricted by limited tumor specificity and sensitivity due to off-tumor signal leakage and a lower content of the targets. Therefore, a self-powered and self-recycled strategy based on molecular beacon (MB) hybridized on tetrahedral framework DNA (E-MB-tFNA) using the endogenous enzyme, apurinic/apyrimidinic endonuclease 1 (APE1), was rationally developed for tumor cell-specific molecular imaging with superior spatial specificity and improved sensitivity. The apurinic/apyrimidinic site (AP site) can be specifically recognized and cleaved by APE1, and was modified on the stem and loop region of E-MB-tFNA. The resultant E-MB-tFNA can be specifically recognized and cleaved by APE1 in the cytoplasm, which is overexpressed in tumor cells compared to normal cells. In particular, once APE1 cleaves the AP site on the stem region (double-stranded DNA) of E-MB-tFNA, the self-powered and self-recycled sequences modified on the stem region of E-MB-tFNA is freed to hybridize with the loop region of E-MB-tFNA, prompting APE1 to further hydrolyze the E-MB-tFNA loop region and generate fluorescence signals. In addition, the self-powered and self-recycled sequences can be hybridized with other E-MB-tFNA to continuously and cyclically amplify the fluorescence signal. The experimental results of this study showed that the E-MB-tFNA has the capability to monitor drug resistance and achieve guided precision surgical excision in vivo with superior spatial specificity and improved sensitivity. In particular, E-MB-tFNA can realize the risk classification of neuroblastoma patients in clinical plasma.
研究领域:
生物医学工程
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分子生物学
·
肿瘤学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Mengxin Zhang,Yingyu Zhang,Xianwei Zhang,Kangbo Liu,Lifeng Li,Zhidan Yu,Jingya Yuan,Wancun Zhang
Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.
研究领域:
生物化学
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分子生物学
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医学影像学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Mengxin Zhang,Yingyu Zhang,Qionglin Wang,Kangbo Liu,Lifeng Li,Zhidan Yu,Ligong Hou,Xianwei Zhang,Huan Zhao,Weyland Cheng,Wancun Zhang
In situ imaging of microRNA (miRNA) content and distribution is valuable for monitoring tumor progression. However, tumor specific in situ imaging remains a challenge due to low miRNA abundance, lack of biological compatibility, and poor specificity. In this study, we designed a DNA tetrahedral framework complex with hairpins (DTF-HP AP ) consisting of an apurinic/apyrimidinic site (AP site) that could be specifically recognized and cleaved by apurinic/apyrimidinic endonuclease 1 (APE1). Efficient and specific in situ imaging of miR-21 in tumors was thus achieved through catalytic hairpin assembly (CHA) reaction. In this study, DTF-HP AP was successfully constructed to trigger the cumulative amplification of fluorescence signal in situ . The specificity, sensitivity and serum stability of DTF-HP AP were verified in vitro , and DTF-HP AP could be easily taken up by cells, acting as a biosensor to detect tumors in mice. Furthermore, we verified the ability of DTF-HP AP to specifically image miR-21 in tumors, and demonstrated its capability for tumor-specific imaging in clinical samples.
研究领域:
分子生物学
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生物医学工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Jingbo Sun,Liushunhao Chen,Hongchen Li,Chen Xu,Dong Xu,Jiali Ren
Biological staining is essential for imaging, functional investigation, and disease diagnostics. In this research, innovative green-emissive carbon dots (G-CDs) were hydrothermally prepared from 1,2,4-triaminobenzene and ascorbic acid (AA) and further explored for versatile imaging of mammalian cells, plant cells, and microorganisms. The G-CDs, exhibiting fluorescence enhancement, outperform conventional dyes in terms of staining efficiency and specificity across various biological systems. For mammalian cells (SH-SY5Y, Hep3B, and HEK293), the G-CDs can stain both the nuclei and nucleoli in 10 min via a micropinocytic endocytosis approach, with the latter brighter. Fluorescence enhancement was greater for RNA than for DNA. Interestingly, for plant cells, only cell walls were stained, because positive charges on G-CDs enable strong adsorption onto the negatively charged cell walls, thereby hindering their further entry. G-CDs can stain cell walls and nuclei for fungi (including Aspergillus flavus and Aspergillus niger ), and cell walls and nucleoids for bacteria ( Bacillus subtilis and Escherichia coli ). The targeted staining arises from both the binding of G-CDs to DNA, RNA, pectin, peptidoglycan, and cellulose, and fluorescence enhancement due to surface passivation inhibiting rotation and vibration of functional groups. Electrostatic interactions, coordination, hydrogen bonding, and amidation collectively account for the interactions between G-CDs and these biomolecules . Finally, their practical applications in leucorrhea examinations demonstrated their capability to differentiate between bacterial and fungal vaginosis, highlighting their potential in clinical diagnostics.
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Xingkang Diao,GuoHua Qi,Xinli Li,Yu Tian,Jing Li,Yongdong Jin
Cell cycle analysis is crucial for disease diagnosis and treatment, especially for investigating cell heterogeneity and regulating cell behaviors. Exosomes are highly appealing as noninvasive biomarkers for monitoring real-time changes in the cell cycle due to their abundant molecular information inherited from their metrocyte cells and reflecting the state of these cells to some extent. However, to our knowledge, the relationship between exosomes and the cell cycle has not been reported. Herein, we successfully monitored the variation of exosomal surface-enhanced Raman spectroscopy (SERS) spectra to discriminate different cell cycle stages (G0/G1, S, and G2/M phases) based on label-free surface-enhanced Raman spectroscopy (SERS) combined with the machine learning method of linear discriminant analysis (LDA). An average accuracy of 85% based on the trained SERS spectra of exosomes from different cell cycle stages confirmed the high reliability of the support vector machine (SVM) algorithm for analyzing dynamic changes in the cell cycle at different time points. Importantly, the related molecular mechanisms among mitotic processes (prometaphase, metaphase, and anaphase/telophase) and unique biomolecular events between cancerous (HeLa) and normal (H8) cells were also revealed by the present label-free SERS detection platform. Based on SERS analysis, the content of phenylalanine (Phe) within HeLa cells increased, and some structures of proteins containing Phe and tryptophan (Trp) residues may be transformed during the mitotic process. Notably, the α-helix and β-sheet of proteins coexisted in HeLa cells; meanwhile, the α-helix of the proteins was more dominant in H8 cells than in HeLa cells. The strategy is effective for discriminating cell cycle stages and elucidating the associated molecular events during the cell mitotic process and will provide potential application value for guiding the cell cycle treatment strategies of cancer in the future.
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PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yang Chen,Wenzhe Xu,Hao Jin,Mengsi Zhang,Shuwei Liu,Yi Liu,Hao Zhang
Heterogeneous reprogrammed nutrient metabolic networks formed by oncogenes exhibit the potential for exploring novel druggable targets and developing innovative anticancer therapeutics. Herein, based on the heterogeneous metabolic characteristics of glutamine (Gln) addiction in pancreatic cancer cells, an iron-delivery system (IDS) with enhanced endocytosis is designed for efficient ferroptosis therapy. The IDS is characterized by Gln modification and can be recognized as a source of Gln nutrients for efficient endocytic uptake by pancreatic tumor cells. Because the IDS is flexible to combine with amino acid-like components, the IDS with enhanced endocytosis is further produced by loading the Gln transporter inhibitor of V9302. V9302 is capable of suppressing molecular Gln uptake via transporter ASCT2, which generates Gln deprivation to direct metabolic reprogramming of cancer cells and enhances cellular uptake of Gln-modified IDS via RAS-stimulated macropinocytosis. The enhanced endocytosis and high iron content of IDS facilitate ferroptosis in mice pancreatic tumor models; thus, an amino acid-like ferroptosis inducer of l-buthionine sulfoximine (BSO) is further combined. The enhanced endocytosis resulting from the synergism of Gln and V9302 enables the efficient delivery of iron and BSO for ferroptosis tumor therapy. This work provides an alternative approach for enhancing intracellular drug delivery of the tumors with heterogeneous nutrient metabolism by virtue of combining nutrient-modified nanodrugs with the corresponding nutrient transporter inhibitors.
研究领域:
肿瘤学
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药学
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生物医学工程
·
癌症代谢
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Yue Wang,Ping Wang,Haiyan Li,Xiaoran Han,Haibin Zhu,Xiangqun Jin
To improve the oral absorption and anticancer efficacy of the BCS-IV drug etoposide (ETO), oral nanocrystal-loaded lipid carriers (Lipo@NCs) were developed in this study by modifying the BCS-IV drug nanocrystal with the lipid bilayer. The ETO-Lipo@NCs were prepared by the thin film hydration high-pressure homogenization method, and the core of positively charged ETO nanocrystals was prepared by the sonoprecipitation-high pressure homogenization method. The optimized ETO-Lipo@NCs were spherical particles with an average particle size of 220.3 ± 14.2 nm and a zeta potential of −9.95 ± 0.81 mV, respectively. The successful coating of a lipid bilayer on the surface of nanocrystals in ETO-Lipo@NCs was confirmed by several characterization methods. Compared to nanocrystals, the release rate and degree of Lipo@NCs in SIF were significantly decreased, indicating that the lipid bilayer can effectively prevent the rapid dissolution of core nanocrystals. ETO-Lipo@NCs demonstrated a significant improvement in the intestinal permeability and absorption of ETO in a single intestinal perfusion experiment. In the cells, ETO-Lipo@NCs showed enhanced cellular uptake and transepithelial transport compared with ETO nanocrystals. Pharmacokinetic analysis indicated that ETO-Lipo@NCs had a longer plasma half-life than ETO solution, and the oral bioavailability of ETO-Lipo@NCs was 1.96- and 10.92-fold higher than that of ETO nanocrystals and ETO coarse crystals, respectively. Moreover, the ETO-Lipo@NCs orally dosed at 10 mg/kg exhibited an excellent inhibitory effect against tumors in a subcutaneous Lewis lung carcinoma (LLC) xenograft model compared with other preparations. These results indicate that the Lipo@NCs formulation has an oral absorption-promoting effect of the BCS-IV drug ETO, which could warrant further application in the oral delivery of other poorly bioavailable drugs.
研究领域:
药剂学
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肿瘤学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Dan Yang,Yuqi Feng,Ying Yuan,Linxuan Zhang,Yao Zhou,Adam C. Midgley,Yanrong Wang,Ning Liu,Guoliang Li,Xiaolin Yao,Dechun Liu
The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an “active PC” to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of “passive PCs” formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.
研究领域:
纳米技术
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药学
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生物医学工程
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细胞生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
BMEMat
·
2026
·
IF 17.2
Jingwen Xie,Jingxing Si,Xiaobei Deng,Jing Tan,Ruijie Zhu,Jizhou Qi,Gaoxia Ma,Bin Wang,Yi Wang,Yunzhou Guo,Yuping Chen,Shiqun Shao,Youqing Shen
Intranasal administration presents a direct, non-invasive pathway for delivering small interfering RNA (siRNA) to glioblastoma (GBM), but its efficiency is hampered by intranasal and intratumoral barriers. To overcome these barriers, here, we develop a multipotent nanocage system featuring a crosslinked yet reactive oxygen species (ROS)-cleavable, zwitterionic poly (tertiary amine oxide) (PTAO) shell for efficient intranasal siRNA delivery. This design ensures ultrastable siRNA encapsulation under physiological conditions while enabling traceless siRNA release selectively in tumor cells with elevated ROS levels. Notably, the gene silencing efficacy of the nanocages remains unaffected after 1 month of room-temperature storage in solution. By leveraging the zwitterionic property of PTAO, the nanocages exhibit prolonged intranasal residence and enhanced mucus penetration. Furthermore, they induce lipid raft-dependent macropinocytosis and subsequent transcytosis that promotes brain accumulation via the trigeminal nerve pathway and enables deep tumor penetration. This endocytosis mechanism directs nanocages into the non-degradative endoplasmic reticulum-Golgi pathway for intracellular trafficking, bypassing lysosomal trapping. In an orthotopic GBM mouse model, intranasal administration of nanocages loading PLK1 siRNA significantly suppressed glioma growth and extended survival without obvious safety issues. Our study demonstrates the potential of the nanocage platform as an intranasal delivery vehicle, promising broad therapeutic applications in GBM and other neurological disorders.
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产品关联
DOI
高影响因子
NanoImpact
·
2025
·
IF 5.5
Yuan-Yuan Liu,Jie Liu,Yuan Guo,Qiangqiang Zhang,Aoneng Cao,Haifang Wang
Nanoplastics enter the human body mainly by ingestion through the gastrointestinal tract and thus the uptake and release of nanoplastics in intestinal cells have been studied. However, the fate of nanoplastics in intestinal cells remains poorly understood, particularly how they are exocytosed. Herein, we investigated the uptake, distribution, and exocytosis of nanoplastics in Caco-2 cells using 70 nm red fluorescent polystyrene (R70PS) as a nanoplastic model. The results show that R70PS readily enters Caco-2 cells and the content per cell peaks at around 24 h, but the total intracellular content in all cells increases continuously over 72 h. In addition, the uptake mechanisms change over incubation time, i.e. R70PS entered Caco-2 cells via both the energy-independent pathway and the energy-dependent caveolae-mediated endocytosis and macropinocytosis at 4 h incubation, but almost all R70PS entered cells in an energy-dependent manner via caveolae-mediated endocytosis, macropinocytosis, and clathrin-mediated endocytosis at 12 h incubation. Most of the intracellular R70PS accumulated in lysosomes, but R70PS also entered the mitochondria and its level increased over time. Approximately 45 % of the intracellular R70PS could be cleared from the cells within 12 h, mainly via the lysosomal pathway. Exocytosis was also associated with autophagy and was facilitated by the increase in the number of mitochondria and lysosomes, but inhibited by serum in the medium. Our findings deepen the understanding of the interaction between nanoplastics and intestinal cells, which is helpful for the risk assessment of nanoplastics.
研究领域:
生物学
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医学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-24
·
IF 15.7
Zheng Liu-Ting,Yan Zeng-Shuai,Li Xin-Yue,Chang Jia-Jia,Tan Xiao-Qi,Wang Yu-Xing,Ding Hong-Ming,Liu Qin,Ma Yu-Qiang,Huo Da
Membraneless organelles form by phase separation and regulate cell behavior. We show that cholesterol-patterned AuNPs program nanomaterial-induced stress granules (NSGs) by lowering G3BP1 condensation barriers through a solid–liquid–liquid triphasic sequence: nanomaterials recruit hnRNPC, which then engages G3BP1 to nucleate gel-like condensates. We map NSG microenvironments (temperature, polarity, pH, and proteasome activity), uncover dual disassembly—a slow VCP/19S-dependent route and a rapid SUMO/20S-dependent backup—and show that NSGs remodel chemo-plasticity: they mitigate doxorubicin/cisplatin toxicity in normal tissues yet sensitize tumors to nocodazole in vivo. Local induction and selective dissolution of NSGs thus offers a strategy to decouple efficacy from toxicity. Our results establish design rules linking nanomaterial surface chemistry to condensate programming and provide actionable levers to steer therapeutic outcomes.
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）