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ANALYST · 2019 ·Vol. 145 ·期 1 ·107-114 · IF 4.019

Detection of breast cancer-derived exosomes using the horseradish peroxidase-mimicking DNAzyme as an aptasensor

Yu Zhou,Huiying Xu,Hua Wang,Bang-Ce Ye

Exosomes are membrane-enclosed phospholipid extracellular vesicles with a variety of tumor antigens which can be applied in the diagnosis and treatment of cancer due to the high secretion on the surface of cancer cells. Until now, many research studies on exosomes have been reported, but convenient and low-cost detection methods still need to be developed. Recently, we have developed a sensitive, simple and low-cost colorimetric aptasensor by designing a hairpin-like structure, which combined the highly specific MUC1 aptamer with a hemin/G-quadruplex for the detection of breast cancer exosomes. The hemin/G-quadruplex toward H2O2 reduction was used to generate an evidently strong colorimetric response owing to acting as a HRP-mimicking DNAzyme. The aptasensor is regarded as an “on–off” type switch, which strictly controls the process of reaction responding to the existence or not of exosomes. In our study, associated exosome detection limits are 3.94 × 105 particles per mL, which showed a higher sensitivity compared to commercial ELISA. Our method not only exhibited the advantages of being convenient and time-saving, with few instruments used, but also the signal generated using this method can be easily observed by the naked eye. Furthermore, the proposed strategy can well differentiate breast cancer patients from healthy individuals, demonstrating potential application in the analysis of clinical specimens.

CAS / MDL: 9005-64-5
研究领域: 癌症生物学 · 分析化学 · 生物技术 · 医学诊断
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Advanced Healthcare Materials · 2019 ·Vol. 8 ·期 20 ·1900791 · IF 6.27

Tumor Antigen Mediated Conformational Changes of Nanoplatform for Activated Photodynamic Therapy

Junjie Liu,Yiwen Zhang,Wei Liu,Kaixiang Zhang,Jinjin Shi,Zhenzhong Zhang

Photodynamic therapy (PDT) is a noninvasive powerful tool for tumor treatment. However, phototoxicity seriously limits the clinical application of PDT, and activated PDT specifically response to tumor cell antigen is rarely reported. Herein, a tumor cell specific “switch-on” PDT nanoplatform, which employs a well-designed hairpin structure mucl protein (MUC1) aptamer (Apt) as specific linker to conjugate gold nanorod and Chlorin e6 (Ce6) (GNR/Apt-Ce6) is prepared, and “switch on” via conformational changes of aptamer-induced fluorescence resonance energy transfer missing between GNR and Ce6 for selective tumor therapy. In the absence of tumor cells, MUC1 Apt keeps a hairpin structure, leading to Ce6 closely adhered to the surface of GNR, PDT is in an “off” state even under the irradiations. On the contrary, in the presence of tumor cells with overexpressed MUC1, Apt specifically recognizes and binds to MUC1, resulting in conformational changes of Apt from regular hairpin to extended chain structure. Thus with an enlarged distance between Ce6 and GNR, PDT is switched-on. GNR/Apt-Ce6 shows excellent PDT efficacy in tumor-bearing mice (55.1% vs 1.3%, tumor apoptosis rate of GNR/Apt-Ce6 vs GNR/random sequence-Ce6) due to its high tumor-targeting and “switch-on” properties. The strategy of tumor antigen activated PDT is expected to provide a new perspective for clinical application.

CAS / MDL: 1306-38-3
研究领域: 癌症生物学 · 纳米技术 · 治疗学
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Telomerase-Responsive CRISPR System-Regulated Nanobomb for Triggering Research on Telomerase “Self-Detonation”

Wenyue Zhang,Ziyi Li,Xiaoli Lun,Yingshu Guo

Targeting tumor markers is one of the most important approaches to tumor therapy, and the “suicide” pattern of tumor marker response is a very challenging study. Telomerase, as one of the key factors associated with human longevity and cancer progression, is considered to be an emerging biomarker for cancer diagnosis. The targeted drug delivery nanobomb─BIBR1532@HSN/FQDNA/MUC1 aptamer (B@HDA) is prepared in this study based on hollow silica nanoparticles (HSN) and CRISPR systems. Amino-modified FQDNA and amino-modified MUC1 aptamer are covalently attached to the surface of carboxyl-functionalized HSN. The modified MUC1 aptamer directs the nanobomb to specifically target breast cancer cells (MCF-7) and FQDNA sequesters the telomerase inhibitor (BIBR1532) within the HSN. Telomerase primers (TPs) is recognized by the highly expressed telomerase in MCF-7 cells and is elongated to form DNA substrates. The substrate pairs with crRNA bases to effectively activate CRISPR-Cas12a. The activated CRISPR-Cas12a precisely cut FQDNA, releasing BIBR1532, which inhibits telomerase activity. This strategy achieves telomerase “suicide”. The nanobomb described above has the following advantages. (1) The “closing” effect of FQDNA contributes to reducing the nonspecific release of BIBR1532. (2) B@HDA, combined with CRISPR, regulates mitochondrial dysfunction and cell senescence in MCF-7 cells. (3) In the tumor-bearing mouse model, B@HDA, combined with CRISPR, exhibits good biocompatibility and an obvious tumor ablation effect on MCF-7 tumors, suggesting potential application prospects across a wide range of cancer cell lines. In summary, the proposed nanobomb provides a tunable switch approach for the specific inhibition of telomerase and the reduction of tumor cell growth, representing a promising avenue for promoting senescence and treating cancer.

研究领域: 癌症研究 · 分子生物学 · 纳米技术 · 基因工程
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RSC Advances · 2023 ·Vol. 13 ·期 16 ·11215-11224 · IF 3.9

Aptamer modified Zr-based porphyrinic nanoscale metal–organic frameworks for active-targeted chemo-photodynamic therapy of tumors

Haidi Feng,Lu Zhao,Zhiqiang Bai,Zhihui Xin,Chaoyu Wang,Lizhen Liu,Jinping Song,Haifei Zhang,Yunfeng Bai,Feng Feng

Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.

CAS / MDL: 65-85-0 13520-92-8
研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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