Size controlled protein nanoemulsions for active targeting of folate receptor positive cells

Ana Loureiro, Eugénia Nogueira, Nuno G. Azoia, Marisa P. Sárria, Ana S. Abreu, Ulyana Shimanovich, Alexandra Rollett, Johan Härmark, Hans Hebert, Georg Guebitz, Gonçalo J.L. Bernardes, Ana Preto, Andreia C. Gomes, Artur Cavaco-Paulo

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Bovine serum albumin (BSA) nanoemulsions were produced by high pressure homogenization with a tri-block copolymer (Poloxamer 407), which presents a central hydrophobic chain of polyoxypropylene (PPO) and two identical lateral hydrophilic chains of polyethylene glycol (PEG). We observed a linear correlation between tri-block copolymer concentration and size - the use of 5. mg/mL of Poloxamer 407 yields nanoemulsions smaller than 100. nm. Molecular dynamics and fluorescent tagging of the tri-block copolymer highlight their mechanistic role on the size of emulsions. This novel method enables the fabrication of highly stable albumin emulsions in the nano-size range, highly desirable for controlled drug delivery. Folic Acid (FA)-tagged protein nanoemulsions were shown to promote specific folate receptor (FR)-mediated targeting in FR positive cells. The novel strategy presented here enables the construction of size controlled, functionalized protein-based nanoemulsions with excellent characteristics for active targeting in cancer therapy.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalColloids and Surfaces B: Biointerfaces
Volume135
DOIs
StatePublished - 1 Nov 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier B.V..

Funding

Ana Loureiro (SFRH/BD/81479/2011) and Eugénia Nogueira (SFRH/BD/81269/2011) hold scholarships from Fundação para a Ciência e a Tecnologia (FCT). Gonçalo J. L. Bernardes is a Royal Society University Research Fellow at the Department of Chemistry, University of Cambridge and an Investigador FCT at the Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa. We thank Patrícia Nogueira, Jaime Freitas, Alexandra Moreira and Alexandre M. Carmo from Instituto de Biologia Molecular e Celular (IBMC) by the cellular experiments using primary activated human macrophages. We also thank Bruno Fernandes for technical assistance in experiments of nanoparticle stability in biological medium. This work has received funding from the European Union Seventh Framework Programme ( FP7/2007-2013 ) under grant agreement NMP4-LA-2009-228827 NANOFOL. This work was supported by FEDER through POFC – COMPETE and by Portuguese funds from FCT through the project PEst-OE/BIA/UI4050/2014. The authors also thank the FCT Strategic Project of UID/BIO/04469/2013 unit.

FundersFunder number
Eugénia NogueiraSFRH/BD/81269/2011
Seventh Framework Programme228827, NMP4-LA-2009-228827 NANOFOL
Fundação para a Ciência e a Tecnologia
Seventh Framework Programme
European Regional Development FundUID/BIO/04469/2013, PEst-OE/BIA/UI4050/2014

    Keywords

    • Active targeting
    • Folic acid
    • High pressure homogenization
    • PEGylated surfactant
    • Protein-based nanoemulsions

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