Octa-arginine boosts the penetration of elastin-like polypeptide nanoparticles in 3D cancer models

Lisanne M.P.E. van Oppen, Jan Pille, Christiaan Stuut, Marleen van Stevendaal, Lisa N. van der Vorm, Jan A.M. Smeitink, Werner J.H. Koopman, Peter H.G.M. Willems, Jan C.M. van Hest, Roland Brock (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Elastin-like polypeptide (ELP) nanoparticles are a versatile platform for targeted drug delivery. As for any type of nanocarrier system, an important challenge remains the ability of deep (tumor) tissue penetration. In this study, ELP particles with controlled surface density of the cell-penetrating peptide (CPP) octa-arginine (R8) were created by temperature-induced co-assembly. ELPs formed micellar nanoparticles with a diameter of around 60 nm. Cellular uptake in human skin fibroblasts was directly dependent on the surface density of R8 as confirmed by flow cytometry and confocal laser scanning microscopy. Remarkably, next to promoting cellular uptake, the presence of the CPP also enhanced penetration into spheroids generated from human glioblastoma U-87 cells. After 24 h, uptake into cells was observed in multiple layers towards the spheroid core. ELP particles not carrying any CPP did not penetrate. Clearly, a high CPP density exerted a dual benefit on cellular uptake and tissue penetration. At low nanoparticle concentration, there was evidence of a binding site barrier as observed for the penetration of molecules binding with high affinity to cell surface receptors. In conclusion, R8-functionalized ELP nanoparticles form an excellent delivery vehicle that combines tunability of surface characteristics with small and well-defined size.

Original languageEnglish
Pages (from-to)175-184
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume137
DOIs
Publication statusPublished - 1 Apr 2019

Fingerprint

Cell-Penetrating Peptides
Elastin
Nanoparticles
Arginine
Peptides
Neoplasms
Cell Surface Receptors
Glioblastoma
Confocal Microscopy
Flow Cytometry
Fibroblasts
Binding Sites
Skin
Temperature
Pharmaceutical Preparations

Keywords

  • Binding site barrier
  • Elastin-like polypeptide nanoparticles
  • Octa-arginine
  • Penetration
  • Spheroid
  • Humans
  • Microscopy, Confocal/methods
  • Oligopeptides/chemistry
  • Elastin/chemistry
  • Drug Delivery Systems
  • Nanoparticles
  • Cell-Penetrating Peptides/chemistry
  • Flow Cytometry
  • Spheroids, Cellular/metabolism
  • Time Factors
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical/methods
  • Binding Sites
  • Glioblastoma/metabolism

Cite this

van Oppen, L. M. P. E., Pille, J., Stuut, C., van Stevendaal, M., van der Vorm, L. N., Smeitink, J. A. M., ... Brock, R. (2019). Octa-arginine boosts the penetration of elastin-like polypeptide nanoparticles in 3D cancer models. European Journal of Pharmaceutics and Biopharmaceutics, 137, 175-184. https://doi.org/10.1016/j.ejpb.2019.02.010
van Oppen, Lisanne M.P.E. ; Pille, Jan ; Stuut, Christiaan ; van Stevendaal, Marleen ; van der Vorm, Lisa N. ; Smeitink, Jan A.M. ; Koopman, Werner J.H. ; Willems, Peter H.G.M. ; van Hest, Jan C.M. ; Brock, Roland. / Octa-arginine boosts the penetration of elastin-like polypeptide nanoparticles in 3D cancer models. In: European Journal of Pharmaceutics and Biopharmaceutics. 2019 ; Vol. 137. pp. 175-184.
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abstract = "Elastin-like polypeptide (ELP) nanoparticles are a versatile platform for targeted drug delivery. As for any type of nanocarrier system, an important challenge remains the ability of deep (tumor) tissue penetration. In this study, ELP particles with controlled surface density of the cell-penetrating peptide (CPP) octa-arginine (R8) were created by temperature-induced co-assembly. ELPs formed micellar nanoparticles with a diameter of around 60 nm. Cellular uptake in human skin fibroblasts was directly dependent on the surface density of R8 as confirmed by flow cytometry and confocal laser scanning microscopy. Remarkably, next to promoting cellular uptake, the presence of the CPP also enhanced penetration into spheroids generated from human glioblastoma U-87 cells. After 24 h, uptake into cells was observed in multiple layers towards the spheroid core. ELP particles not carrying any CPP did not penetrate. Clearly, a high CPP density exerted a dual benefit on cellular uptake and tissue penetration. At low nanoparticle concentration, there was evidence of a binding site barrier as observed for the penetration of molecules binding with high affinity to cell surface receptors. In conclusion, R8-functionalized ELP nanoparticles form an excellent delivery vehicle that combines tunability of surface characteristics with small and well-defined size.",
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van Oppen, LMPE, Pille, J, Stuut, C, van Stevendaal, M, van der Vorm, LN, Smeitink, JAM, Koopman, WJH, Willems, PHGM, van Hest, JCM & Brock, R 2019, 'Octa-arginine boosts the penetration of elastin-like polypeptide nanoparticles in 3D cancer models', European Journal of Pharmaceutics and Biopharmaceutics, vol. 137, pp. 175-184. https://doi.org/10.1016/j.ejpb.2019.02.010

Octa-arginine boosts the penetration of elastin-like polypeptide nanoparticles in 3D cancer models. / van Oppen, Lisanne M.P.E.; Pille, Jan; Stuut, Christiaan; van Stevendaal, Marleen; van der Vorm, Lisa N.; Smeitink, Jan A.M.; Koopman, Werner J.H.; Willems, Peter H.G.M.; van Hest, Jan C.M.; Brock, Roland (Corresponding author).

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 137, 01.04.2019, p. 175-184.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Octa-arginine boosts the penetration of elastin-like polypeptide nanoparticles in 3D cancer models

AU - van Oppen, Lisanne M.P.E.

AU - Pille, Jan

AU - Stuut, Christiaan

AU - van Stevendaal, Marleen

AU - van der Vorm, Lisa N.

AU - Smeitink, Jan A.M.

AU - Koopman, Werner J.H.

AU - Willems, Peter H.G.M.

AU - van Hest, Jan C.M.

AU - Brock, Roland

PY - 2019/4/1

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N2 - Elastin-like polypeptide (ELP) nanoparticles are a versatile platform for targeted drug delivery. As for any type of nanocarrier system, an important challenge remains the ability of deep (tumor) tissue penetration. In this study, ELP particles with controlled surface density of the cell-penetrating peptide (CPP) octa-arginine (R8) were created by temperature-induced co-assembly. ELPs formed micellar nanoparticles with a diameter of around 60 nm. Cellular uptake in human skin fibroblasts was directly dependent on the surface density of R8 as confirmed by flow cytometry and confocal laser scanning microscopy. Remarkably, next to promoting cellular uptake, the presence of the CPP also enhanced penetration into spheroids generated from human glioblastoma U-87 cells. After 24 h, uptake into cells was observed in multiple layers towards the spheroid core. ELP particles not carrying any CPP did not penetrate. Clearly, a high CPP density exerted a dual benefit on cellular uptake and tissue penetration. At low nanoparticle concentration, there was evidence of a binding site barrier as observed for the penetration of molecules binding with high affinity to cell surface receptors. In conclusion, R8-functionalized ELP nanoparticles form an excellent delivery vehicle that combines tunability of surface characteristics with small and well-defined size.

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