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    Awakening p53 in vivo by D-peptides-functionalized ultra-small nanoparticles: Overcoming biological barriers to D-peptide drug delivery

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    Author
    Bian, Z.
    Yan, J.
    Wang, S.
    Date
    2018
    Journal
    Theranostics
    Publisher
    Ivyspring International Publisher
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.7150/thno.27165
    Abstract
    Peptides are a rapidly growing class of therapeutics with many advantages over conventional small molecule drugs. Dextrorotary (D)-peptides, with increased enzymatic stability and prolonged plasma half-life in comparison with natural L-peptides, are considered to have great potential as recognition molecules and therapeutic agents. However, the in vivo efficacy of current therapeutic D-peptides is hindered by their inefficient cellular uptake in diseased tissues. Methods: To overcome physiological and cellular barriers to D-peptides, we designed a gold-based ultra-small nanocarrier coupled with polylysine (PLL) and a receptor-targeted peptide to deliver therapeutic D-peptides. Using a D-peptide p53 activator (DPA) as a proof of concept, we synthesized, functionalized and characterized gold- and DPA-based nanoparticles termed AuNP-DPA. Results: AuNP-DPA were effectively enriched in tumor sites and subsequently internalized by cancer cells, thereby suppressing tumor growth via reactivating p53 signaling. More importantly, through a series of in vivo experiments, AuNP-DPA showed excellent biosafety without the common side effects that hinder p53 therapies in clinic trials. Conclusion: The present study not only sheds light on the development of AuNP-DPA as a novel class of antitumor agents for drugging the p53 pathway in vivo, but also supplies a new strategy to use D-peptides as intracellular PPI inhibitors for cancer-targeted therapy. Copyright Ivyspring International Publisher.
    Sponsors
    This work was supported by the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University (No. XJTU1AF-CRF-2017-003 to P. H. and W. H.). The authors gratefully acknowledge financial support from the China Scholarship Council (to W. H. and J. Y.) and thank Prof. Bert Vogelstein (Ludwig Center at John Hopkins, USA) for kindly providing the human colon cancer cell HCT116 p53-/- cell line with both p53 alleles deleted.
    Keyword
    Biosafety
    Dextrorotary peptide
    Gold nanoparticle
    p53
    Ultra-small nanoparticle
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056753121&doi=10.7150%2fthno.27165&partnerID=40&md5=f25f9052e1a80bf18135f321c9613fab; http://hdl.handle.net/10713/9662
    ae974a485f413a2113503eed53cd6c53
    10.7150/thno.27165
    Scopus Count
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    UMB Open Access Articles 2018

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