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Biomaterials Science · 2019 ·Vol. 7 ·期 9 ·3652-3661 · IF 5.251

Fabricating an intelligent cell-like nano-prodrug via hierarchical self-assembly based on the DNA skeleton for suppressing lung metastasis of breast cancer

Yunyan Li,Tong Yan,Wenya Chang,Chongjiang Cao,Dawei Deng

Cancer metastasis is a major cause of high mortality in breast cancer. Despite the progress achieved in nanomaterial-based treatments, the cure rate remains unsatisfactory, owing to their poor biocompatibility and non-specific recognition. Inspired by the cell-mimetic strategy, in this work, we fabricated an intelligent cell-like nano-prodrug (Dox-MPK@MDL) for lung metastasis of breast cancer. Specifically, a DNA tetrahedron dendrimer was selected to act as a rigid internal cytoskeleton, and then sequentially coated with a liposome and macrophage membrane to form cell-like Dox-MPK@MDL via hierarchical self-assembly. Here, it should be noted that pH-sensitive Dox-MPK prodrugs were synthesized and inserted into the DNA-based cytoskeleton (the Dox group is an intercalator of double stranded DNA) in advance for the next anti-metastatic therapy. Our results show that Dox-MPK@MDL specifically targeted the sites of lung metastasis via the biomimetic metastasis-homing effects and intelligently triggered Dox release at the metastatic cancer cells, thereby leading to the significant inhibition of lung metastasis. All these features help to enhance the anti-metastatic therapy efficiency of Dox while maximally reducing side-effects.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 药物科学
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 12 ·1-9 · IF 5.479

DNA-scaffold copper nanoclusters integrated into a cerium(III)-triggered Fenton-like reaction for the fluorometric and colorimetric enzymatic determination of glucose

Li Hui,Lu Yuexiang,Pang Jiawei,Sun Jingwei,Yang Fengyi,Wang Ziyi,Liu Yueying

A fluorometric and colorimetric method are described for the determination of hydrogen peroxide and glucose by integrating copper nanoclusters (CuNCs) into a Fenton-like reaction. The mechanism mainly depends on the fast formation of long-strand DNA-templated CuNCs with strong red fluorescence (with excitation/emission maxima at 340/640 nm) in the absence of H 2 O 2 . The DNA can be cleaved into short-oligonucleotide fragments by hydroxy radicals as formed in the Ce(III)-triggered Fenton-like reaction in the presence of H 2 O 2 . As a result, short-strand DNA loses the ability as a template for the formation of CuNCs. This leads to a decrease of fluorescence. The colorimetric assay, in turn, is based on the oxidation of colorless Ce(III) ions to the distinctly yellow Ce(IV) ions (with an absorption maximum at 400 nm) by H 2 O 2 . Compared with those assays based on the use of enzyme mimics, this method does not require any chromogenic substrates such as ABTS and TMB. Based on the dual-signal readout platform, we successfully achieved the detection of H 2 O 2 and glucose. LODs are as low as 0.266 μM and 2.92 μM. The methods were applied to the sensitive determination of glucose by using glucose oxidase (GOx) which catalyzes the oxidization of glucose to produce H 2 O 2 . The practical application was demonstrated by determination of glucose in human serum, with apparent recoveries of 98.4–101.9% and 99.1–105.6%, respectively. The concentration of glucose ranges from 1 to 500 μM and 50 to 600 μM based on the dual-signal readout platform, respectively. This fluorometric and colorimetric dual-mode strategy will pave a new avenue for constructing effective assays for H 2 O 2 -related analytes in biochemical and clinical applications. Schematic representation of a fluorometric and colorimetric dual-readout strategy for the sensitive determination of hydrogen peroxide and glucose. The assay has been designed by integrating copper nanoclusters into a Ce(III)-triggered Fenton-like reaction.

研究领域: 分析化学 · 生物化学 · 临床诊断
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