Coating Nanoparticles with Plant-Produced Transferrin-Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells

Lauri J. Reuter, Mohammad-Ali Shahbazi, Ermei M. Mäkilä, Jarno J. Salonen, Reza Saberianfar, Rima Menassa, Hélder A. Santos, Jussi J. Joensuu, Anneli Ritala

    Research output: Contribution to journalArticleScientificpeer-review

    29 Citations (Scopus)

    Abstract

    The encapsulation of drugs to nanoparticles may offer a solution for targeted delivery. Here, we set out to engineer a self-assembling targeting ligand by combining the functional properties of human transferrin and fungal hydrophobins in a single fusion protein. We showed that human transferrin can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV. Transferrin-HFBIV was further expressed in tobacco BY-2 suspension cells. Both partners of the fusion protein retained their functionality; the hydrophobin moiety enabled migration to a surfactant phase in an aqueous two-phase system, and the transferrin moiety was able to reversibly bind iron. Coating porous silicon nanoparticles with the fusion protein resulted in uptake of the nanoparticles in human cancer cells. This study provides a proof-of-concept for the functionalization of hydrophobin coatings with transferrin as a targeting ligand.
    Original languageEnglish
    Pages (from-to)1639-1648
    JournalBioconjugate Chemistry
    Volume28
    Issue number6
    DOIs
    Publication statusPublished - 2017
    MoE publication typeA1 Journal article-refereed

    Funding

    We acknowledge financial support from the Academy of Finland grants 252215, 252442, 281300 and Centre of Excellence Programme HYBER. We also thank the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013, grant no. 310892). Funding from the Academy of Finland also enabled a very beneficial researcher exchange between VTT and Agriculture and Agrifood Canada. The Electron Microscopy Unit of the Institute of Biotechnology, University of Helsinki is thanked for providing the laboratory facilities and assistance.

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