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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2019 · IF 2.931

A new “turn-on” fluorescence probe based on hydrazine-triggered tandem reaction

Wenzhi Xu,Xue Li,Mengnan Han,Tingting Zhou,Yutao Yang,Wei Li

Hydrazine is extremely harmful to the human body. The leakage of hydrazine is liable to cause potential safety hazards. Here, we reported a new fluorescence probe based on the tandem reaction . The hydrazine-triggered hydrazinolysis-cyclization resulted in the formation of the iminocoumarin. The fluorescence intensity at 522 nm of the probe increased after the reaction with hydrazine. There was a linear relationship between the fluorescence intensity and the concentration of hydrazine (0.14–120.00 μM). The LOD of the probe to N 2 H 4 was 1.36 ppb. Notably, the probe could detect hydrazine in BT474 cells and tap water.

研究领域: 分析化学 · 环境科学 · 生物医学

✓ 已验证 DOI PubMed 高影响因子

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DRUG DELIVERY · 2018 · IF 3.095

Doxorubicin conjugated with a trastuzumab epitope and an MMP-2 sensitive peptide linker for the treatment of HER2-positive breast cancer

Yiwen You,Zhiyuan Xu,Yun Chen

HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH2 (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDYCDGFYACYMDV-NH2, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX via a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as in vitro model systems and nude mice with BT474 xenografts as an in vivo model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower in vitro IC50, and its in vivo extent of inhibition in mice was more evident. During this process, enzymatic cleavage of MAHNP-DOX is critical for its activation and cellular uptake. In addition, a synergistic response was observed after the combination of DOX and AHNP. This effect was probably due to the involvement of AHNP in the PI3K–AKT signaling pathway, which can be largely activated by DOX and leads to anti-apoptotic signals.

CAS / MDL: 141-78-6 108-55-4 148893-10-1 76-05-1 60-29-7

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

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A new “turn-on” fluorescence probe based on hydrazine-triggered tandem reaction

Doxorubicin conjugated with a trastuzumab epitope and an MMP-2 sensitive peptide linker for the treatment of HER2-positive breast cancer