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Transferrin Adsorption onto PLGA Nanoparticles Governs Their Interaction with Biological Systems from Blood Circulation to Brain Cancer Cells

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ABSTRACT

Purpose

Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells.

Methods

NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors.

Results

While slightly modifying size (80 to 90 nm) and zeta potential (−44 to −32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs in vitro. Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors.

Conclusion

Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.

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Acknowledgments & DISCLOSURES

We would like to thank Pierre Legras from the Service Commun d’Animalerie Hospitalo-Universitaire (SCAHU) d’Angers, france for technical support. Archibald Paillard received a PhD fellowship from Le Comité Départemental de Maine-et-Loire de la Ligue Contre le Cancer. This work was supported by La Ligue Nationale Contre le Cancer through an Equipe Labellisée 2007 grant and by the Cancéropôle Grand-Ouest. We would also like to thank Mike Howsam for careful reading of the manuscript.

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Authors and Affiliations

  1. EA 4483, Laboratoire de physiologie, Université de Lille 2, Lille, France

    Jiang Chang & Didier Betbeder

  2. Université d’Artois, Arras, France

    Jiang Chang & Didier Betbeder

  3. LUNAM Université, Université d’Angers Ingénierie de la Vectorisation Particulaire, Angers, France

    Archibald Paillard, Catherine Passirani, Marie Morille, Jean-Pierre Benoit & Emmanuel Garcion

  4. INSERM, U646, Angers, France

    Archibald Paillard, Catherine Passirani, Marie Morille, Jean-Pierre Benoit & Emmanuel Garcion

  5. Inserm U646, IBS – CHU Angers, 4 rue Larrey, 49933, Angers cedex 9, France

    Emmanuel Garcion

  6. EA 4483, Faculté de Médecine Pôle Recherche, Laboratoire de Physiologie, 1 place de Verdun, 59000, Lille, France

    Didier Betbeder

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  1. Jiang Chang
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  2. Archibald Paillard
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  3. Catherine Passirani
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Correspondence to Didier Betbeder or Emmanuel Garcion.

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J. Chang and A. Paillard contributed equally to this work.

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Chang, J., Paillard, A., Passirani, C. et al. Transferrin Adsorption onto PLGA Nanoparticles Governs Their Interaction with Biological Systems from Blood Circulation to Brain Cancer Cells. Pharm Res 29, 1495–1505 (2012). https://doi.org/10.1007/s11095-011-0624-1

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  • DOI: https://doi.org/10.1007/s11095-011-0624-1

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