PolyMetformin combines carrier and anticancer activities for in vivo siRNA delivery View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-06-06

AUTHORS

Yi Zhao, Wei Wang, Shutao Guo, Yuhua Wang, Lei Miao, Yang Xiong, Leaf Huang

ABSTRACT

Metformin, a widely implemented anti-diabetic drug, exhibits potent anticancer efficacies. Herein a polymeric construction of Metformin, PolyMetformin (PolyMet) is successfully synthesized through conjugation of linear polyethylenimine (PEI) with dicyandiamide. The delocalization of cationic charges in the biguanide groups of PolyMet reduces the toxicity of PEI both in vitro and in vivo. Furthermore, the polycationic properties of PolyMet permits capture of siRNA into a core-membrane structured lipid-polycation-hyaluronic acid (LPH) nanoparticle for systemic gene delivery. Advances herein permit LPH-PolyMet nanoparticles to facilitate VEGF siRNA delivery for VEGF knockdown in a human lung cancer xenograft, leading to enhanced tumour suppressive efficacy. Even in the absence of RNAi, LPH-PolyMet nanoparticles act similarly to Metformin and induce antitumour efficacy through activation of the AMPK and inhibition of the mTOR. In essence, PolyMet successfully combines the intrinsic anticancer efficacy of Metformin with the capacity to carry siRNA to enhance the therapeutic activity of an anticancer gene therapy. More... »

PAGES

11822

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    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms11822

    DOI

    http://dx.doi.org/10.1038/ncomms11822

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032452479

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27264609


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