ANALYST
·
2020
·Vol. 145
·期 10
·3557-3563
·
IF 3.978
Hui Zhang,Bin Qiao,Qunqun Guo,Juqian Jiang,Chenxin Cai,Jian Shen
Facile detection of tumour-derived extracellular vesicles (EVs) is crucial to cancer diagnosis. Herein, a facile and label-free electrochemical aptasensor was fabricated to detect tumour-derived EVs based on the target-induced proximity hybridization of split aptamers. In this assay, two designed oligonucleotide probes containing fragments of a protein tyrosine kinase-7 (PTK7) aptamer were used to recognize and capture EVs containing PTK7. In the presence of target EVs, the aptamer–target ternary complex could induce proximity hybridization and form a DNA duplex on the electrode. The DNA duplex could bind more electroactive Ru(NH3)63+ through electrostatic attraction, resulting in an increased cathodic current signal. By virtue of the excellent electrochemical signal reporter RuHex, the specificity of the aptamer and proximity ligation, a facile EV electrochemical aptasensor with a detection limit of 6.607 × 105 particles per mL was realized. Furthermore, this aptasensor showed good selectivity to distinguish different tumour-derived EVs and was applied to detect EVs in complex biological samples. The proposed electrochemical aptasensor can be further extended to the detection of other EVs, thus showing great potential in clinical diagnosis.
研究领域:
生物医学工程
·
癌症诊断
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-17
·
IF 52.7
Su Minhui,Liu Yuan,Lin Hongxin,Wang Xiaoxing,Ying Danxia,Zhang Lizhuan,Yang Cai,Jiang Mengyuan,Xu Lujuan,Wang Xie,Sun Yang,Xu Haiyan,Zhang Ziwen,Wang Xiaojia,Fu Ting,Xie Sitao,He Jiaxuan,Liu Xiangsheng,Tan Weihong
Aptamers serve as unique targeting ligands, making aptamer-drug conjugates (ApDCs) an attractive strategy for targeted cancer therapy. This study performs a comprehensive evaluation from rodents to non-human primates (NHP) of a protein tyrosine kinase 7 (PTK7)-targeted ApDC (Sgc8c-M) made by conjugating the potent antimitotic agent monomethyl auristatin E (MMAE) to the classic PTK7 aptamer Sgc8c. Efficacy studies in various cancer types with PTK7 overexpression showed that Sgc8c-M effectively induces sustained tumor regression in cell line-derived and patient-derived xenografts, outperforming unconjugated MMAE, the chemotherapy drug paclitaxel, and a PTK7-targeted antibody-drug conjugate. Pharmacokinetic (PK) studies in mice revealed that Sgc8c-M leads to rapid accumulation and sustained MMAE levels in tumors, along with fast clearance from plasma and normal tissues. Further study in rats confirmed rapid clearance across most organs and revealed that over 75% of MMAE was excreted through urine and feces within 24 h. Toxicokinetic (TK) assessments indicated comparable systemic drug exposure without accumulation for repeated doses compared to single administration. Toxicity evaluations showed that the therapeutic dose with high efficacy was safe and that the toxicity resulting from extremely high doses could be reversibly controlled. Encouraged by these findings, we evaluated PK/TK profiles and safety of Sgc8c-M in cynomolgus monkeys. Similar to PK/TK profiles observed in rats, Sgc8c-M demonstrated good dose-dependent drug exposure. It was, moreover, well tolerated in monkeys with no obvious accumulation following multiple administrations. These findings highlight the potential of Sgc8c-M as an effective antitumor agent and provide useful insights for the clinical translation of emerging ApDCs.
研究领域:
肿瘤学
·
药物代谢
·
转化医学
·
分子靶向治疗
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生物药剂学
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毒理学
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临床前药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemosensors
·
2023
·Vol. 11
·期 7
·415
·
IF 4.2
Die Sun,Qunqun Guo,Hui Zhang,Chenxin Cai
Tumor cell-derived exosomes are considered a potential source of cancer biomarkers. Here, we developed an electrochemical sensing platform for the rapid and simple detection of exosomes, using the CCRF-CEM exosome as a model. The platform utilizes cyclic nicking enzyme cleavage and a hybridization chain reaction (HCR) for dual-signal amplification. A hairpin aptamer probe (HAP) containing an aptamer was designed for the assay. The specific binding between the aptamer and PTK7, present on the exosome surface, causes a conformational change in the HAP. This facilitates hybridization between the HAP and the linker DNA, which subsequently triggers cyclic cleavage of the nicking endonuclease towards the linker DNA. Therefore, exosome detection is transformed into DNA detection. By combining this approach with HCR signal amplification, we achieved high-sensitivity electrochemical detection of CCRF-CEM exosomes, down to 1.1 × 104particles/mL. Importantly, this assay effectively detected tumor exosomes in complex biological fluids, demonstrating the potential for clinical diagnosis.Keywords:exosomes;electrochemistry;cyclic enzyme scission;hybridization chain reaction
研究领域:
生物医学工程
·
癌症研究
·
分子生物学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Materials Advances
·
2022
·Vol. 3
·期 18
·7080-7086
·
IF 0
Xueke Wu,Chenyuan Yan,Lixuan Mu,Yuan Wang,Guangwei She,Wensheng Shi
By assembling fluorophore-marked DNA stem-loops on the surface of gold nanobipyramids (AuNBPs) with an efficient photothermal conversion, we fabricated a multifunctional photothermal reagent (AuNBPs-mPEG/AA-TR). The sgc8 sequences that were embedded inside the DNA stem-loops can specifically target the PTK7, an overexpressed protein located on the surface of CCRF-CEM cells (human acute lymphoblastic leukemia T lymphocyte) to realize an active targeting function. Before the AuNBPs-mPEG/AA-TR bind to the PTK7 proteins, the DNA stem-loops are folded, and the fluorophore linked on the DNA stem-loop will be close to the AuNBPs. In this configuration, the fluorescence from the fluorophore is quenched by the AuNBPs. However, when the AuNBPs-mPEG/AA-TR bound to the PTK7 proteins through the sgc8 sequences, the DNA stem-loops can be opened partially to enable the fluorophore to be far away from the AuNBPs. As a result, the fluorescent signal will be activated. Therefore, the fluorescence can be used as a visual signal to reveal the binding between the AuNBPs-mPEG/AA-TR and CCRF-CEM cells (usually called activatable fluorescence labelling). While under irradiation of an 808 nm laser, the CCRF-CEM cells could be ablated through the photothermal therapy of the AuNBPs-mPEG/AA-TR with a high photothermal efficiency. Applying the AuNBPs-mPEG/AA-TR to Human B lymphoma cells (Ramos cells) and CCRF-CEM cells, we found that only the CCRF-CEM cells can be effectively targeted, actively fluorescently labeled, and readily ablated by the AuNBPs-mPEG/AA-TR. This work provides an alternative photothermal agent for the targeted therapy of tumors.
研究领域:
纳米技术
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生物医学工程
·
癌症治疗
·
分子生物学
·
光学
✓ 已验证
DOI
危险品化学品经营许可证（带存储）