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

doi:10.1021/acs.bioconjchem.7b00075

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

University of Helsinki
Technical University of Denmark (DTU)
University of Turku
London Research and Development Centre

Research output: Contribution to journal › Article › Scientific › peer-review

33 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 language	English
Pages (from-to)	1639-1648
Journal	Bioconjugate Chemistry
Volume	28
Issue number	6
DOIs	https://doi.org/10.1021/acs.bioconjchem.7b00075
Publication status	Published - 2017
MoE publication type	A1 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1021/acs.bioconjchem.7b00075

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

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.",

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AU - Reuter, Lauri J.

AU - Shahbazi, Mohammad-Ali

AU - Mäkilä, Ermei M.

AU - Salonen, Jarno J.

AU - Saberianfar, Reza

AU - Menassa, Rima

AU - Santos, Hélder A.

AU - Joensuu, Jussi J.

AU - Ritala, Anneli

PY - 2017

Y1 - 2017

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AB - 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.

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DO - 10.1021/acs.bioconjchem.7b00075

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SP - 1639

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JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 6

ER -

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

Abstract

Funding

UN SDGs

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