Dataset Information

Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring ?-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease.

ABSTRACT: Development of sensitive detectors of A? aggregates and effective inhibitors of A? aggregation are of diagnostic importance and therapeutic implications for Alzheimer's disease (AD) treatment. Herein, a novel strategy has been presented by self-assembly of peptide conjugated Au nanorods (AuP) as multifunctional A? fibrillization detectors and inhibitors. Our design combines the unique high NIR absorption property of AuNRs with two known A? inhibitors, A?15-20 and polyoxometalates (POMs). The synthesized AuP can effectively inhibit A? aggregation and dissociate amyloid deposits with NIR irradiation both in buffer and in mice cerebrospinal fluid (CSF), and protect cells from A?-related toxicity upon NIR irradiation. In addition, with the shape and size-dependent optical properties, the nanorods can also act as effective diagnostic probes to sensitively detect the A? aggregates. This is the first report to integrate 3 segments, an A?-targeting element, a reporter and inhibitors, in one drug delivery system for AD treatment.

SUBMITTER: Li M

PROVIDER: S-EPMC5566101 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring β-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease.

Li Meng M Guan Yijia Y Zhao Andong A Ren Jinsong J Qu Xiaogang X

Theranostics 20170722 12

Development of sensitive detectors of Aβ aggregates and effective inhibitors of Aβ aggregation are of diagnostic importance and therapeutic implications for Alzheimer's disease (AD) treatment. Herein, a novel strategy has been presented by self-assembly of peptide conjugated Au nanorods (AuP) as multifunctional Aβ fibrillization detectors and inhibitors. Our design combines the unique high NIR absorption property of AuNRs with two known Aβ inhibitors, Aβ15-20 and polyoxometalates (POMs). The syn ...[more]

PMID: 28839459

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Project description:Investigation of targeting inhibitors of A? aggregation, heme-A? peroxidase-like activity and efficient detectors of A? aggregation, are of therapeutic value and diagnostics significance for the treatment of Alzheimer's disease (AD). Due to the complex pathogenesis of AD, theranostics treatment with multiple functions are necessary. Herein we constructed the NIR absorption property of gold nanorods (GNRs) loaded with single chain variable fragment (scFv) 12B4 and thermophilic acylpeptide hydrolase (APH) ST0779 as a smart theranostic complex (GNRs-APH-scFv, GAS), which possesses both rapid detection of A? aggregates and NIR photothermal treatment that effectively disassembles A? aggregates and inhibits A?-mediated toxicity. Methods: We screened targeting anti-A? scFv 12B4 and thermophilic acylpeptide hydrolase as amyloid-degrading enzyme, synthesized GAS gold nanorods complex. The GAS was evalued by A? inhibition and disaggregation assays, A? detection assays, A? mediated toxicity assays in vitro. In vivo, delaying A?-induced paralysis in AD model of Caenorhabditis elegans was also tested by GAS. Results: In vitro, GAS has a synergistic effect to inhibit and disassociate A? aggregates, in addition to decrease heme-A? peroxidase-like activity. In cultured cells, treatment with GAS reduces A?-induced cytotoxicity, while also delaying A?-mediated paralysis in CL4176 C.elegans model of AD. Furthermore, the photothermal effect of the GAS upon NIR laser irradiation not only helps disassociate the A? aggregates but also boosts APH activity to clear A?. The GAS, as a targeting detector and inhibitor, allows real-time detection of A? aggregates. Conclusion: These results firstly highlight the combination of scFv, APH and nanoparticles to be theranostic AD drugs. Taken together, our strategy provides a new thought into the design of smart compounds for use as efficiently therapeutic and preventive agents against AD. Moreover, our design provides broad prospects of biomedical strategy for further theranostics application in those diseases caused by abnormal protein.

Dataset Information

Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring ?-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease.

Publications

Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring β-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease.

Similar Datasets

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