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Biocompatibility study of two diblock copolymeric nanoparticles for biomedical applications by in vitro toxicity testing

  • Felipe Goñi-de-Cerio
  • Valentina Mariani
  • Dror Cohen
  • Lea Madi
  • Julie Thevenot
  • Hugo Oliveira
  • Chiara Uboldi
  • Guido Giudetti
  • Rosella Coradeghini
  • Elisabeth Garanger
  • François Rossi
  • Meital Portugal-Cohen
  • Miriam Oron
  • Rafi Korenstein
  • Sébastien Lecommandoux
  • Jessica Ponti
  • Blanca Suárez-Merino
  • Pedro HerediaEmail author
Research Paper

Abstract

Drugs used for chemotherapy normally carry out adverse, undesired effects. Nanotechnology brings about new horizons to tackle cancer disease with a different strategy. One of the most promising approaches is the use of nanocarriers to transport active drugs. These nanocarriers need to have special properties to avoid immune responses and toxicity, and it is critical to study these effects. Nanocarriers may have different nature, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as low toxicity. Little has been done regarding specific nanocarriers toxicity. In this study, we performed a thorough toxicological study of two different block copolymer nanoparticles (NPs); poly(trimethylene carbonate)-block–poly(l-glutamic acid) (PTMC-b–PGA) and poly(ethylene glycol)-block–poly(γ-benzyl-l-glutamate) (PEG-b–PBLG) with sizes between 113 and 131 nm. Low blood–serum–protein interaction was observed. Moreover, general toxicity assays and other endpoints (apoptosis or necrosis) showed good biocompatibility for both NPs. Reactive oxygen species increased in only two cell lines (HepG2 and TK6) in the presence of PTMC-b–PGA. Cytokine production study showed cytokine induction only in one cell line (A549). We also performed the same assays on human skin organ culture before and after UVB light treatment, with a moderate toxicity after treatment independent of NPs presence or absence. Interleukin 1 induction was also observed due to the combined effect of PEG-b–PBLG and UVB light irradiation. Future in vivo studies for biocompatibility and toxicity will provide more valuable information, but, so far, the findings presented here suggest the possibility of using these two NPs as nanocarriers for nanomedical applications, always taking into account the application procedure and the way in which they are implemented.

Keywords

Amphiphilic copolymers Nanoparticles In vitro toxicity Cancer therapy Nanoparticles toxicity Biomedicine 

Notes

Acknowledgments

This study was supported by the European Commission FP7 Programme 2007–2013 under NANOTHER project (www.nanother.eu), Grant Agreement Number CP-IP 213631-2 NANOTHER. We want to particularly acknowledge the patients enrolled in the blood serum study for their participation and the Basque Biobank for Research-OEHUN for its collaboration.

Supplementary material

11051_2013_2036_MOESM1_ESM.docx (30 kb)
Supplementary material 1 (DOCX 31 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Felipe Goñi-de-Cerio
    • 1
  • Valentina Mariani
    • 2
  • Dror Cohen
    • 6
    • 7
  • Lea Madi
    • 5
  • Julie Thevenot
    • 3
    • 4
  • Hugo Oliveira
    • 3
    • 4
  • Chiara Uboldi
    • 2
  • Guido Giudetti
    • 2
  • Rosella Coradeghini
    • 2
  • Elisabeth Garanger
    • 3
    • 4
  • François Rossi
    • 2
  • Meital Portugal-Cohen
    • 6
  • Miriam Oron
    • 6
  • Rafi Korenstein
    • 5
  • Sébastien Lecommandoux
    • 3
    • 4
  • Jessica Ponti
    • 2
  • Blanca Suárez-Merino
    • 1
  • Pedro Heredia
    • 1
    Email author
  1. 1.GAIKER Technology CentreVizcayaSpain
  2. 2.Nanobiosciences Unit, Institute for Health and Consumer Protection, Joint Research CentreEuropean CommissionIspraItaly
  3. 3.Université de BordeauxENSCPBPessac CedexFrance
  4. 4.CNRS, LCPOUMR 5629Pessac CedexFrance
  5. 5.Department of Physiology and Pharmacology, Sackler School of MedicineTel-Aviv UniversityTel AvivIsrael
  6. 6.AHAVADead Sea LaboratoriesLodIsrael
  7. 7.The Dead Sea Laboratory for Biochemistry and Biotechnology of the SkinDead Sea and Arava Science CenterEin-GediIsrael

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