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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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Yujing Liang,Yifei Wang,Mengdi Yu,Yuqian Jiang,Jinhua Shang,Xiaoqing Liu,Fuan Wang
Biomolecules play essential roles in regulating the orderly progression of biochemical reaction networks. DNA-based biocircuits supplement an attractive and ideal approach for the visual imaging of endogenous biomolecules, yet their sensing performance is commonly encumbered by the undesired signal leakage. To solve this issue, here we proposed a glutathione (GSH)-activated DNA circuit for achieving the spatio-selective microRNA imaging through the successive response of a GSH-specific activation procedure and a non-enzymatic catalytic signal amplification procedure. In this design, by incorporating a disulfide bond into the pre-sealed nucleic acid probe, the uncontrolled circuitry leakage could be effectively ameliorated. In target cancer cells with high-abundant GSH and miR-21, endogenous GSH recognized and cleaved the pre-installed disulfide bond within DNA probes, thereby restoring the activity of circuitry components. The miR-21 then catalyzed the specific operation of circuitry for generating an amplified readout signal. We demonstrate that this system not only enables the effective discriminations of various cell types, but also contributes to the exploration of the correlationship between GSH and miR-21. This on-site activated DNA circuit can be extended to the robust analysis and exploration of different biomolecular interactions, offering a reliable reference for the in-depth understanding of biochemical interaction networks.
研究领域:
生物化学
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分子生物学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Sheng Yang,Jiaxing Jiang,Anxin Zhou,Yibo Zhou,Wenling Ye,Dong-Sheng Cao,Ronghua Yang
Tyrosinase (TYR) is a crucial enzyme involved in melanogenesis, and its overexpression is closely associated with melanoma. To precisely monitor intracellular TYR activity, remote control of a molecule imaging tool is highly meaningful but remains to be explored. In this work, we present the first photocaged tyrosinase fluorogenic probe by caging the substrate of the enzymatic probe with a photolabile group. Because of the sequential light and enzyme-activation feature, this probe exhibits photocontrollable “turn on” response toward TYR with good selectivity and high sensitivity (detection limit: 0.08 U/mL). Fluorescence imaging results validate that the caged probe possesses the capability of visualizing intracellular endogenous tyrosinase activity in a photocontrol fashion, thus offering a promising molecule imaging tool for investigating TYR-related physiological function and pathological role. Moreover, our sequential activation strategy has great potential for developing more photocontrollable enzymatic fluorogenic probes with spatiotemporal resolution.
研究领域:
生物化学
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医学影像
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细胞生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Weiwei Zeng,Zhuoyao Wu,Yan Xu,Weitao Yang,Bingbo Zhang
Molecular magnetic resonance imaging (mMRI) of biomarkers is essential for accurate cancer detection in precision medicine. However, the current clinically used contrast agents provide structural magnetic resonance imaging (sMRI) information only and rarely provide mMRI information. Here, a tumor-specific furin-catalyzed nanoprobe (NP) was reported for differential diagnosis of malignant breast cancers (BCs) in vivo. This NP with a compact structure of Fe3O4@Gd-DOTA NPs (FFG NPs) contains an “always-on” T2-weighted MR signal provided by the magnetic Fe3O4 core and a furin-catalyzed enhanced T1-weighted MR signal provided by the Gd-DOTA moiety. The FFG NPs were found to produce an activated T1 signal in the presence of furin catalysis and an “always-on” T2 signal, providing mMRI and sMRI information simultaneously. Ratiometric mMRI:sMRI intensity can be used for differential diagnosis of malignant BCs MDA-MB-231 and MCF-7, where the furin levels relatively differ. The proposed probe not only provides structural imaging but also enables real-time molecular differential visualization of BC through enzymatic activities of cancer tissues.
研究领域:
医学影像学
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肿瘤学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
OPTICS EXPRESS
·
2025
·Vol. 33
·期 9
·20023-20036
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IF 3.3
Yuhan Nie,Yuhan Nie,Jie Hu,Siying Zhang,Xiangzhou Meng,Xiangzhou Meng,Guo Fu,Guo Fu,Guo Fu
Single-molecule localization microscopy (SMLM) breaks the diffraction limit, significantly enhancing optical resolution and providing a powerful tool for imaging complex biological structures in life sciences. However, imaging biological structures below 10 nm and studying protein-protein interactions remains a challenge for optical super-resolution microscopy. Here, we introduce a microscopy based on two-color single-molecule localization microscopy, we call it molecular Imaging by two-color imaging (MITI), which improves resolution to the molecular level, reaching several nanometers. We demonstrate MITI is suitable for samples labeled with organic dyes and photoactivatable/photoswichable fluorescent proteins. MITI can resolve two dyes separated by ssDNA with 2-10 nm length as well as ffDronpa and PAmCherry1 fused to the N- and C-terminal of FtsZ (ffDronpa-FtsZ-PAmCherry1). MITI is versatile and easy to realize, and thus, it will expand the applications of molecular scale super-resolution microscopy in life sciences.
研究领域:
生物物理学
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细胞生物学
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显微技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ULTRASOUND IN MEDICINE
·
2025
·
IF 2.4
Likang Hou,Zhili Guo,Shun Liu,Xiaowen Liang,Meng Du,Zhiyi Chen
Objectives To assess the severity of intrauterine adhesion (IUA) after endometrial injury via ultrasound molecular imaging (USMI) of vascular endothelial growth factor receptor 2 (VEGFR2) expression on the uterine endothelium. Methods MB VEGFR2 was constructed via “biotin-avidin-biotin” bridging technology. A rat IUA animal model was constructed via chemical injury. Fourteen days after the model was constructed, MB Con and MB VEGFR2 contrast agents were injected into the standard group and the model group of rats, and simultaneous ultrasound molecular imaging was carried out and ultrasound molecular imaging was performed and the changes in ultrasound signals in vivo were normalized to differential targeted enhancement (dTE). In addition, immunohistochemistry was used to detect the expression levels of VEGFR2 and α-SMA in the uterine tissues of the rats in both groups. Results Targeted-VEGFR2 microbubble (MB VEGFR2 ) was successfully constructed, the average particle size of the targeted VEGFR2 microbubble contrast agent was 2309.6 ± 234.3 nm, with the average zeta potential -16.9 ± 0.15 mV and the dispersity coefficient less than 0.4. In addition, its essential performance and biosafety were examined, which revealed that the MB VEGFR2 contrast agent had an appropriate size, stable imaging performance, good target adhesion, and good biocompatibility. In vivo, ultrasound imaging results revealed that after the injection of the targeted MB VEGFR2 , the contrast ultrasound signal intensity of uterine tissues in the model group (62.5 ± 17.9 dB) was higher than in the normal group (33.5 ± 12.5 dB), and the difference was statistically significant ( P < .05). The immunohistochemistry results revealed that the expression of VEGFR2 and α-SMA in the uterine tissue of the model group was greater than that in the standard group ( P < .05), further indicating that the signal intensity of the MB VEGFR2 contrast agent can reflect the expression level of VEGFR2 molecules. Conclusions Ultrasound molecular imaging based on MB VEGFR2 can be used to evaluate the expression level of VEGFR2 in uterine vascular endothelial cells. This provides a potential approach for the early diagnosis and treatment monitoring of intrauterine adhesions after endometrial injury.
研究领域:
医学影像学
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生殖医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 10
·4481
·
IF 13.3
Yupeng Sun,Rui Li,Yike Cai,Yan Liu,Peiyuan Wang,Ming Wu,Xiaolong Zhang,Naishun Liao,Cuilin Zhang,Aixian Zheng,Haipo Xu,Rui Zeng,Yongyi Zeng,Xiaolong Liu
Tumor-infiltrating CD8 + T cells and programmed death-1 (PD1) levels are critical indicators for tumor immunophenotyping and therapeutic decision-making. Noninvasive optical imaging in the second near infrared window (NIR-II) is particularly well-suited for investigating the biological processes within tumors in live mammals, thanks to its deep-tissue penetration and superior spatiotemporal resolution. However, in vivo NIR-II imaging has primarily been restricted to a single probe at a time. Methods: Herein, we developed a two-plex NIR-II molecular imaging method utilizing the non-overlapping fluorescence emission of indocyanine green (ICG) in the NIR-IIa window (1000-1200 nm) and PbS/CdS core-shell quantum dots (QDs) in the NIR-IIb window (1500-1700 nm). By integrating PD1 aptamer-labeled ICG (ICG-Apt-PD1, targeting PD1) and CD8 aptamer-labeled QDs (QDs@Apt-CD8, targeting CD8 + T cells), our two-plex NIR-II molecular imaging enabled simultaneous and noninvasive monitoring of the number of CD8 + T cells and PD1 levels in tumors. Results: QDs@Apt-CD8 demonstrated the excellent ability for in vivo imaging of tumor infiltrating CD8 + T cells, owing to its strong NIR-IIb luminescence and the high selectivity and specificity. This two-plex in vivo molecular imaging allowed for dynamic monitoring for PD1 levels and the number of CD8 + T cells in tumors. We observed the heterogeneous bio-distributions of PD1 and CD8 + T cells across different tumor types and revealed the tumor immunophenotypes. Moreover, our findings indicated that the low PD1 and high CD8 + T cells levels in tumors predicted a better anti-tumor effect. Conclusions: Such in vivo noninvasive NIR-II molecular imaging would complement ex vivo biopsy-based diagnostic techniques, and it could contribute to developing an in vivo tumor immune-scoring algorithm to offer a more precise prediction for immunotherapeutic response.
研究领域:
生物医学工程
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肿瘤免疫学
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分子影像学
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产品关联
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
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肿瘤学
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产品关联
DOI
高影响因子
Advanced Science
·
2018
·Vol. 5
·期 3
·1700392
·
IF 12.441
Yang Wang,Xingyun Liao,Jianguo Sun,Bin Yi,Shenglin Luo,Tao Liu,Xu Tan,Dengqun Liu,Zelin Chen,Xin Wang,Chunmeng Shi
The characterization of cancer stem-like cells (CSCs) has profound implications for elucidating cancer biology and developing treatment strategies. Although surface markers are already used to identify CSCs, the expression of these markers is controversially linked to the phenotypes in different types of tumors and does not represent all functionally relevant of CSCs. Very recently, hyperactive HIF-1α/glycolysis metabolic pathway is recognized as a master regulator of CSCs. In this study, a near-infrared fluorescent small-molecule, IR-780, is identified for the exclusive characterization of human CSCs through the HIF-1α/glycolysis dependent mitochondrial transporter ABCB10's activity. The results identified for the first time that ABCB10 is involved in the preferential uptake of IR-780 in CSCs, which is regulated by HIF-1α via the direct interaction with the binding site of ABCB10 gene promoter region. In addition, IR-780 is demonstrated to conjugate with anticancer drug 5-fluorouracil to act as a potential drug delivery carrier for CSC-targeted therapy. Thus, the studies provide a new rational approach independent of surface markers to characterize CSCs via small-molecule-based imaging of HIF-1α/glycolysis hyperactive metabolic pathway dependent mitochondrial transporter's activity, which holds promise for the further development of CSCs targeted diagnostic and therapeutic strategies.
研究领域:
肿瘤学
·
分子生物学
·
癌症代谢
·
药物递送系统
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Songlin Liu,Bochen Ma,LiQing Qi,Jiantao Ping,YuDong Che,YiMin Zhang,Meng Su,YanLin Song,LuBin Qi,Yifei Jiang,Xiaohong Fang
The rapid and sensitive quantification of low-abundance protein markers holds immense significance in early disease diagnosis and treatment. Single-molecule fluorescence imaging exhibits very high detection sensitivity and thus has great application potential in this area. The single-molecule signal, however, is often susceptible to interference from background noise due to its inherently weak intensity. A variety of signal amplification techniques based on cascading reactions have been developed to improve the signal-to-noise ratio of single-molecule imaging. Nevertheless, the operation of these methods is typically complicated and time-consuming, which limits the clinical application. Herein, we introduce an enzyme-free, photonic-crystal-based single-molecule (PC-SM) biochip for cost-effective, time-efficient, and ultrasensitive detection of disease markers. The PC-SM biochip can enhance the signal-to-noise ratio of single molecules by nearly 3-fold compared with unamplified samples, through coupling of the single-molecule photon energy with the optical band gap of the photonic crystal. We used the PC-SM biochip to detect the low-abundance leukemia inhibitory factor in the blood of pancreatic cancer patients and healthy people and achieved a detection limit of 2.0 pg/L and an AUC of 0.9067. The method exhibits exceptional sensitivity and specificity, showing great application potential in various clinical settings.
研究领域:
生物医学工程
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癌症研究
·
分子诊断
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Zede Wu,Qiuyu Li,Kai Zhu,Shuting Zheng,Honglei Hu,Meirong Hou,Li Qi,Siwen Chen,Yikai Xu,Bingxia Zhao,Chenggong Yan
Immunotherapy has emerged as an innovative strategy with the potential to improve outcomes in cancer patients. Recent evidence indicates that radiation-induced DNA damage can activate the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to enhance the antitumor immune response. Even so, only a small fraction of patients currently benefits from radioimmunotherapy due to the radioresistance and the inadequate activation of the cGAS-STING pathway. Herein, this work integrates hafnium oxide (HfO 2 ) nanoparticles (radiosensitizer) and 7-Ethyl-10-hydroxycamptothecin (SN38, chemotherapy drug, STING agonist) into a polydopamine (PDA)-coated core-shell nanoplatform (HfO 2 @PDA/Fe/SN38) to achieve synergistic chemoradiotherapy and immunotherapy. The co-delivery of HfO 2 /SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS-STING pathway, which then triggers dendritic cells maturation and CD8 + T cells recruitment. Consequently, the growth of both primary and abscopal tumors in tumor-bearing mice is efficiently inhibited. Moreover, the HfO 2 @PDA/Fe/SN38 complexes exhibit favorable magnetic resonance imaging (MRI)/photoacoustic (PA) bimodal molecular imaging properties. In summary, these developed multifunctional complexes have the potential to intensify immune activation to realize simultaneous cancer Radio/Chemo/Immunotherapy for clinical translation.
研究领域:
癌症研究
·
纳米技术
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免疫治疗
·
放射肿瘤学
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分子成像
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Minghui Hu,Yingyu Zhang,Jie Zhang,Xianwei Zhang,Mengxin Zhang,Kangbo Liu,Lifeng Li,Zhidan Yu,Fei Zhang,Wancun Zhang
In vivo optical tumor molecular imaging encounters significant challenges in achieving adequate tumor specificity and sensitivity, largely attributed to off-tumor signal leakage and the relatively low expression levels of target molecules. Therefore, a double self-amplified programmable allosteric DNA nanomachine (named HPs-tFNA) is developed through two elaborately designed hairpin structures (HP1 and HP2) hybridized on tetrahedral framework DNA (tFNA), enabling rapid, specific, and sensitive tumor molecular imaging using the highly specific expression of apurinic/apyrimidinic endonuclease 1 (APE1) in the tumor cytoplasm as a stimulus-response target. In the presence of APE1, HP2 modifies two apurinic/apyrimidinic sites (AP sites), which can be specifically recognized and cleaved by APE1, releasing a significant number of cyclic sequences (cyclic-seq) and achieving initial APE1-assisted signal amplification. Subsequently, cyclic-seq hybridizes with HP1, inducing a conformational change that converts the stem-loop structure of HP1 to a linear form. This structural change facilitates the spatial separation of the fluorophore and quencher, thereby generating fluorescence signals. Furthermore, APE1 incises two AP sites within the HP1 loop region, resulting in the release of cyclic-seq. The released cyclic-seq can hybridize with additional HP1 to continuously amplify the fluorescence signal in a cyclic manner, thereby achieving the second round of signal amplification assisted by APE1. The experimental results of this study demonstrated that HPs-tFNA can achieve rapid in situ tumor molecular imaging and guide precise surgical excision in vivo, with superior spatial specificity. In particular, HPs-tFNA can effectively monitor drug resistance in neuroblastoma cells and stratify risk levels of neuroblastoma via plasma analysis.
研究领域:
生物医学工程
·
分子影像学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）