ANALYTICAL CHEMISTRY
·
2015
·
IF 5.636
Yan-Ran Li,Qian Liu,Zhangyong Hong,He-Fang Wang
For the widely used “off-on” fluorescence (or phosphorescence) resonance energy transfer (FRET or PRET) system, the separation of donors and acceptors species was vital for enhancing the sensitivity. To date, separation of free donors from FRET/PRET inhibition systems was somewhat not convenient, whereas separation of the target-induced far-between acceptors has hardly been reported yet. We presented here a novel magnetic separation-assistant fluorescence resonance energy transfer (MS-FRET) inhibition strategy for highly sensitive detection of nucleolin using Cy5.5-AS1411 as the donor and Fe3O4-polypyrrole core–shell (Fe3O4@PPY) nanoparticles as the NIR quenching acceptor. Due to hydrophobic interaction and π–π stacking of AS1411 and PPY, Cy5.5-AS1411 was bound onto the surface of Fe3O4@PPY, resulting in 90% of fluorescence quenching of Cy5.5-AS1411. Owing to the much stronger specific interaction of AS1411 and nucleolin, the presence of nucleolin could take Cy5.5-AS1411 apart from Fe3O4@PPY and restore the fluorescence of Cy5.5-AS1411. The superparamagnetism of Fe3O4@PPY enabled all separations and fluorescence measurements complete in the same quartz cell, and thus allowed the convenient but accurate comparison of the sensitivity and fluorescence recovery in the cases of separation or nonseparation. Compared to nonseparation FRET inhibition, the separation of free Cy5.5-AS1411 from Cy5.5-AS1411-Fe3O4@PPY solution (the first magnetic separation, MS-1) had as high as 25-fold enhancement of the sensitivity, whereas further separation of the nucleolin-inducing far-between Fe3O4@PPY from the FRET inhibition solution (the second magnetic separation, MS-2) could further enhance the sensitivity to 35-fold. Finally, the MS-FRET inhibition assay displayed the linear range of 0.625–27.5 μg L–1 (8.1–359 pM) and detection limit of 0.04 μg L–1 (0.05 pM) of nucleolin. The fluorescence intensity recovery (the percentage ratio of the final restoring fluorescence intensity to the quenched fluorescence intensity of Cy5.5-AS1411 solution by 0.09 g L–1 Fe3O4@PPY) was enhanced from 36% (for nonseparation) to 56% (for two magnetic separations). This is the first accurate evaluation for the effect of separating donor/acceptor species on the FRET inhibition assay.
研究领域:
生物化学
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Yubo Wang,Yong Zhou,Jinling Wang,Lu Zhang,Chen Liu,Ding Guo,Yanlin Yu,Roumei Ye,Yun Wang,Bing Xu,Yiming Luo,Dengyue Chen
The limited selectivity and high systemic toxicity of traditional chemotherapy hinder its efficacy in treating diffuse large B-cell lymphoma (DLBCL). The combination of sonodynamic therapy (SDT) with chemotherapy has emerged as a novel strategy for cancer treatment, aiming to improve therapeutic outcomes and reduce systemic toxicity. However, challenges such as elevated drug clearance rates and non-selecitivity remain to be resolved. This study has developed a biocompatible nanomedicine delivery system, PA-HM@DOX/ICG, employing hollow mesoporous silica nanoparticles (HMSNs) as the nanocarrier. The nanomedicine incorporates the chemotherapeutic agent doxorubicin (DOX) along with the sonosensitizer indocyanine green (ICG) within its encapsulation, and undergoes additional surface modification using lipid-nucleic acid conjugates (DSPE-PEG-AS1411) to facilitate active targeted delivery. In vitro cellular experiments have validated that PA-HM@DOX/ICG can specifically recognize and be internalized by SU-DHL-4 lymphoma cells due to the overexpression of nucleolin on their surface. The synergistic effects of DOX-induced DNA damage and reactive oxygen species (ROS) generated by ultrasound-activated ICG induce apoptosis in these cells. Furthermore, PA-HM@DOX/ICG displays minimal toxicity towards LO2 normal hepatocytes, indicating a favorable biosafety profile. In vivo animal studies have shown that PA-HM@DOX/ICG effectively accumulates in tumor sites in mice through both the enhanced permeability and retention (EPR) effect and nucleolin-mediated targeting. Under ultrasound irradiation, PA-HM@DOX/ICG significantly inhibits tumor growth. This study introduces a nanoplatform that integrates chemotherapy with sonodynamic therapy, offering a novel approach for the efficient treatment of DLBCL.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemistryOpen
·
2021
·Vol. 10
·期 4
·408-413
·
IF 2.911
Baoqing Liu,Wenzhi Yang,Chengchuan Che,Jinfeng Liu,Meiru Si,Zhijin Gong,Ruixia Gao,Ge Yang
Graphical A nano drug delivery system able to enhance active targeting and therapeutic efficacy has been reported. Nucleic acid aptamer NH 2 -AS1411 (APT) of targeted nucleolin (C23) was used to conjugate on GO-CO-γ-PGA to yield the targeted nano drug delivery system APT-GO-CO-γ-PGA. The structure, composition, dispersion, particle size and morphology properties of the synthesized complex were analyzed via multiple characterization methods to find high drug loading capacity, the ability of controlled and sustained release of drugs, and the targeting to Hela cells. A novel method for the preparation of antitumor drug vehicles has been optimized. Biological materials of chitosan oligosaccharide (CO) and γ-polyglutamic acid (γ-PGA) have previously been employed as modifiers to covalently modify graphene oxide (GO), which in turn loaded doxorubicin (DOX) to obtain a nano drug delivery systems of graphene oxide based composites (GO-CO-γ-PGA-DOX). The system was not equipped with the ability of initiative targeting, thus resulting into toxicity and side effects on normal tissues or organs. In order to further improve the targeting property of the system, the nucleic acid aptamer NH 2 -AS1411 (APT) of targeted nucleolin (C23) was used to conjugate on GO-CO-γ-PGA to yield the targeted nano drug delivery system APT-GO-CO-γ-PGA. The structure, composition, dispersion, particle size and morphology properties of the synthesized complex have been studied using multiple characterization methods. Drug loading and release profile data showed that APT-GO-CO-γ-PGA is provided with high drug loading capacity and is capable of controlled and sustained release of DOX. Cell experimental results indicated that since C23 was overexpressed on the surface of Hela cells but not on the surface of Beas-2B cells, APT-GO-CO-γ-PGA-DOX can target Hela cells and make increase toxicity to Hela cells than Beas-2B cells, and the IC 50 value of APT-GO-CO-γ-PGA-DOX was 3.23±0.04 μg/mL. All results proved that APT-GO-CO-γ-PGA can deliver antitumor drugs in a targeted manner, and achieve the effect of reducing poison, which indicated that the targeted carrier exhibits a broad application prospect in the field of biomedicine.
研究领域:
生物医学工程
·
药学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Xiao Liang,Yudi Wang,Hui Shi,Mengmeng Dong,Haobo Han,Quanshun Li
Background Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.Materials and Methods The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model.Results The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamer-dependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth.Conclusion The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Haofei Ji,Zhilin He,Ying Huang,Xiuen Cao,Qubo Zhu
5-Fluorouracil (5-FU) is a conventional nucleotide analogue used for cancer treatment. However, its clinical application faces challenges such as low stability and non-specific toxicity. With the remarkable advancements in DNA nanotechnology, DNA-based self-assembled nanocarriers have emerged as powerful tools for delivering nucleotide drugs. In this study, we have designed a non-linear hybrid chain reaction involving a fuel strand with AS1411 aptamer sequence to construct a dendritic structure capable of carrying 5-FU. This structure specifically targets cancer cells with overexpressed nucleolin on their surface, allowing the 5-FU to exert its anticancer effects and achieve therapeutic outcomes. Furthermore, we have also investigated the mechanistic action of this drug delivery system, aiming to establish a novel therapeutic platform for 5-FU treatment.
研究领域:
癌症研究
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANNALS OF THE RHEUMATIC DISEASES
·
2024
·
IF 20.3
Fang Qiu,Duoli Xie,Hongzhen Chen,Zhuqian Wang,Jie Huang,Chunhao Cao,Yiying Liang,Xu Yang,Dong-Yi He,Xuekun Fu,Aiping Lu,Chao Liang
Objectives Rheumatoid arthritis (RA) is an autoimmune disease characterised by aggressive fibroblast-like synoviocytes (FLSs). Very few RA patients-derived FLSs (RA-FLSs)-specific surface signatures have been identified, and there is currently no approved targeted therapy for RA-FLSs. This study aimed to screen therapeutic aptamers with cell-targeting and cytotoxic properties against RA-FLSs and to uncover the molecular targets and mechanism of action of the screened aptamers. Methods We developed a cell-specific and cytotoxic systematic evolution of ligands by exponential enrichment (CSCT-SELEX) method to screen the therapeutic aptamers without prior knowledge of the surface signatures of RA-FLSs. The molecular targets and mechanisms of action of the screened aptamers were determined by pull-down assays and RNA sequencing. The therapeutic efficacy of the screened aptamers was examined in arthritic mouse models. Results We obtained an aptamer SAPT8 that selectively recognised and killed RA-FLSs. The molecular target of SAPT8 was nucleolin (NCL), a shuttling protein overexpressed on the surface and involved in the tumor-like transformation of RA-FLSs. Mechanistically, SAPT8 interacted with the surface NCL and was internalised to achieve lysosomal degradation of NCL, leading to the upregulation of proapoptotic p53 and downregulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) in RA-FLSs. When administrated systemically to arthritic mice, SAPT8 accumulated in the inflamed FLSs of joints. SAPT8 monotherapy or its combination with tumour necrosis factor (TNF)-targeted biologics was shown to relieve arthritis in mouse models. Conclusions CSCT-SELEX could be a promising strategy for developing cell-targeting and cytotoxic aptamers. SAPT8 aptamer selectively ablates RA-FLSs via modulating NCL-p53/Bcl-2 signalling, representing a potential alternative or complementary therapy for RA.
研究领域:
免疫学
·
分子生物学
·
治疗学
·
自身免疫疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2020
·
IF 3.807
Xujie Su,Yujie Han,Zhiguang Liu,Lifang Fan,Yujing Guo
Simple, rapid, sensitive, and specific detection of cancer cells plays a pivotal role in the diagnosis and prognosis of cancer. This paper describes an alternative method for detection of nucleolin, which is a major nucleolar protein, overexpressed in several types of cancer, and is a cancer-specific target. Gold nanoparticles/molybdenum disulfide/reduced graphene oxide (AuNPs/MoS 2 /rGO) was easily synthesized with hydrothermal method and characterized by transmission electron microscopy (TEM), x-ray diffraction (XRD) and x-ray photoelectron spectroscopy (XPS). Combining the properties of large surface area and good electrical conductivity of AuNPs/MoS 2 /rGO with the high affinity and specificity of aptamer, a smart hierarchically self-assembled electrochemical aptasensor was established for the specific and sensitive nucleolin (as a model analyte) detection. Under the optimized conditions, AuNPs/MoS 2 /rGO based aptasensor exhibits a great performance for the detection of nucleolin with a linear response from 0.5 nM to 1.0 μM and a low detection limit of 0.16 nM. In addition, this electrochemical aptasensor has good reproducibility towards nucleolin. Besides, the practicability of the TNA (thiolated nucleolin aptamer)/AuNPs/MoS 2 /rGO was demonstrated by analysis of nucleolin in the blood sample. This work paves a promising way for the facile synthesis and design MoS 2 /rGO nanocomposite-based electrochemical aptasensor for testing tumor markers in clinical diagnostics.
研究领域:
分析化学
·
生物医学工程
·
癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Yazhou Huang,Junyan Lv,Lanxiang Gu,Junjie Tao,Songlong Jiao,Yu Zhao,Qun Wang,Guangyun Zhang,Aoyi Cai
Early cancer diagnosis remains a global challenge due to the lack of ultrasensitive and specific detection methods. Herein, we report a dual-active quantum dots (QDs) photoelectrochemical (PEC) sensing platform based on a MoS₂@TaS₂ nano-heterojunction engineered via atomic layer deposition (ALD) for the detection of nucleolin (NCL), a key cancer biomarker. The petal-like MoS₂@TaS₂ nanosheets exhibit enhanced light-harvesting and charge transport properties, as well as a high surface area for uniform QDs loading. This architecture promotes efficient charge separation and suppresses recombination through the synergistic interaction between the heterojunction and CdTe QDs. The resulting sensor achieves a wide linear range (1 fM to 1 nM) and an ultralow detection limit of 0.65 fM, along with excellent specificity and stability. This work offers a promising PEC strategy for early cancer diagnosis.
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Ya Cao,Yuhao Dai,Hong Chen,Yingying Tang,Xu Chen,Ying Wang,Jing Zhao,Xiaoli Zhu
In this work, DNA-templated silver nanoclusters (DNA-AgNCs) with unique fluorescent and electrochemical properties are prepared as dual signal probes for both qualitative imaging and quantitative detection of cancer cells in an integrated system . ITO electrode that has good light transmittance and electric conductivity is employed as a substrate for dual analysis of cancer cells. ITO electrode is firstly modified by AS1141 aptamer , which could selectively bind to nucleolin overexpressed on the surface of a model breast cancer cell, MCF-7 cell line. The composite of mucin 1 antibody (anti-MUC1) and DNA-AgNCs then binds to MUC1 on the surface of captured MCF-7 cell, forming a sandwich-like structure. Therefore, our method allows noninvasive fluorescence imaging and amplified electrochemical detection using a single labeling platform, providing a biocompatible and highly specific method for adequate analysis of cancer cells. Experimental results demonstrate that strong red fluorescence of DNA-AgNCs clearly displays the loading of cancer cells on ITO electrode after dual recognition, and amplified electrochemical signals of DNA-AgNCs enable improved sensitivity toward quantitative analysis with a detection limit of 3 cells.
研究领域:
生物医学工程
·
分析化学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2022
·
IF 7.088
Weigang Chen,Xianhong Cai,Qiang Sun,Xinhua Guo,Chunmei Liang,Hong Tang,Heming Huang,Hui Luo,Lanmei Chen,Jincan Chen
Targeted therapy showed broad application prospects in the treatment of various types of cancer. Through carriers such as aptamers , antibodies, proteins and peptides, targeted therapy can selectively deliver drugs into tumor cells. Compared with traditional treatment methods such as chemo- and radiotherapy, targeted drug delivery systems can reduce the toxic effects of drugs on normal cells and avoid adverse reactions. Herein, an aptamer-cyclometalated iridium(III) complex conjugate (ApIrC) has been designed and developed as a targeted anticancer agent . Owing to the targeting ability of aptamers, ApIrC specifically bound to nucleolin over-expressed on the surface of cancer cells and showed strong fluorescence signal for tumor imaging and diagnosis. ApIrC had more substantial cellular uptake in cancer cells than the iridium complex alone and exhibited favorable low toxicity to normal cells. After uptake by cells through endocytosis , ApIrC can selectively accumulated in mitochondria and induced caspase-3/7-dependent cell death . Remarkably, ApIrC can also specifically target 3D multicellular spheroids (MCSs) and show excellent tumor permeability. So, it can effectively reach the interior of MCSs and cause cell damage. To our knowledge, this is the first report of the aptamer-cyclometalated iridium(III) complex conjugate which studied for cancer targeted therapy. The developed conjugate has great potential to be developed as novel therapeutics for effective and low-toxic cancer treatment.
研究领域:
癌症研究
·
药物化学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 13
·2007391
·
IF 13.281
Xueqi Li,Jianwei Li,Jiarui Xu,Kun Chen,Zhan Zhang,Jialun Duan,Qian Luo,Yafei Du,Songyue Chen,Ying Xie,Wanliang Lu
Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide–lipid derivative (DSPE-PEG 2000 -C 6 -GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT-28nt (containing 17 guanines and 11 thymidines) and DSPE-PEG 2000 -NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer-bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK-STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug-resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide–lipid derivative.
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
分子生物学
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Weicai Wang,Yuanyuan Wang,Minghui Ma,Hyung Jong Jin,Xuemei Li
The construction of completely biocompatible and biodegradable tumor suppressors by a simple and reliable method is essential for the clinical application of cancer-targeted drugs. Herein, by inserting glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) into human serum albumin (HSA) assembly molecules, we constructed a cancer-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT). The modification of HSA could block the GOx activity and reduce the cytotoxicity of normal cells and organs. Through active targeting and passive enhanced permeability and retention effect, the loading of AS1411 could promote the cascade bioreactors to effectively target nucleolin-overexpressed tumors. Once internalized by cancer cells, as a result of catalyzing hydrogen peroxide (H2O2) to produce oxygen (O2), the protein nano-cascade reactor promoted microenvironmental oxygenation, which would subsequently lead to an increase in cytotoxic singlet oxygen (1O2) production under light irradiation as well as the decomposition of intracellular glucose. In vitro and in vivo studies showed that the cascaded nanoreactors could significantly enhance therapeutic efficacy through synergistic starvation therapy and enhanced PDT as well as chemotherapy. This cascade strategy will be demonstrated in clinical applications with huge potential.
研究领域:
癌症研究
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）