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In situ self-assembling Au-DNA complexes for targeted cancer bioimaging and inhibition.

ABSTRACT: Cancer remains one of the most challenging diseases to treat. For accurate cancer diagnosis and targeted therapy, it is important to assess the localization of the affected area of cancers. The general approaches for cancer diagnostics include pathological assessments and imaging. However, these methods only generally assess the tumor area. In this study, by taking advantage of the unique microenvironment of cancers, we effectively utilize in situ self-assembled biosynthetic fluorescent gold nanocluster-DNA (GNC-DNA) complexes to facilitate safe and targeted cancer theranostics. In in vitro and in vivo tumor models, our self-assembling biosynthetic approach allowed for precise bioimaging and inhibited cancer growth after one injection of DNA and gold precursors. These results demonstrate that in situ bioresponsive self-assembling GNC-PTEN (phosphatase and tensin homolog) complexes could be an effective noninvasive technique for accurate cancer bioimaging and treatment, thus providing a safe and promising cancer theranostics platform for cancer therapy.

SUBMITTER: Wang M

PROVIDER: S-EPMC6955332 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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In situ self-assembling Au-DNA complexes for targeted cancer bioimaging and inhibition.

Wang Maonan M Chen Yun Y Cai Weijuan W Feng Huan H Du Tianyu T Liu Weiwei W Jiang Hui H Pasquarelli Alberto A Weizmann Yossi Y Wang Xuemei X

Proceedings of the National Academy of Sciences of the United States of America 20191216 1

Cancer remains one of the most challenging diseases to treat. For accurate cancer diagnosis and targeted therapy, it is important to assess the localization of the affected area of cancers. The general approaches for cancer diagnostics include pathological assessments and imaging. However, these methods only generally assess the tumor area. In this study, by taking advantage of the unique microenvironment of cancers, we effectively utilize in situ self-assembled biosynthetic fluorescent gold nan ...[more]

PMID: 31843938

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Project description:BackgroundSmall interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma.MethodsThis strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded "AND" gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma.ResultsThe proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs.ConclusionsThe endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.

Dataset Information

In situ self-assembling Au-DNA complexes for targeted cancer bioimaging and inhibition.

Publications

In situ self-assembling Au-DNA complexes for targeted cancer bioimaging and inhibition.

Similar Datasets

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