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Article

CPPs to the Test: Effects on Binding, Uptake and Biodistribution of a Tumor Targeting Nanobody

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Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands
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Department of Medical Imaging, Nuclear Medicine, Radboudumc, 6525 GA Nijmegen, The Netherlands
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Department of Biochemistry, Maastricht University, 6229 ER Maastricht, The Netherlands
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Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 293, Bahrain
*
Author to whom correspondence should be addressed.
Academic Editor: Christos Liolios
Pharmaceuticals 2021, 14(7), 602; https://doi.org/10.3390/ph14070602
Received: 4 May 2021 / Revised: 11 June 2021 / Accepted: 15 June 2021 / Published: 23 June 2021
Nanobodies are well-established targeting ligands for molecular imaging and therapy. Their short circulation time enables early imaging and reduces systemic radiation exposure. However, shorter circulation time leads to lower tracer accumulation in the target tissue. Cell-penetrating peptides (CPPs) improve cellular uptake of various cargoes, including nanobodies. CPPs could enhance tissue retention without compromising rapid clearance. However, systematic investigations on how the functionalities of nanobody and CPP combine with each other at the level of 2D and 3D cell cultures and in vivo are lacking. Here, we demonstrate that conjugates of the epidermal growth factor receptor (EGFR)-binding nanobody 7D12 with different CPPs (nonaarginine, penetratin, Tat and hLF) differ with respect to cell binding and induction of endocytosis. For nonaarginine and penetratin we compared the competition of EGF binding and performance of L- and D-peptide stereoisomers, and tested the D-peptide conjugates in tumor cell spheroids and in vivo. The D-peptide conjugates showed better penetration into spheroids than the unconjugated 7D12. Both in vivo and in vitro, the behavior of the agent reflects the combination of both functionalities. Although CPPs cause promising increases in in vitro uptake and 3D penetration, the dominant effect of the CPP in the control of biodistribution warrants further investigation. View Full-Text
Keywords: cell-penetrating peptides; molecular imaging; nanobody; spheroids; tumor targeting; biodistribution cell-penetrating peptides; molecular imaging; nanobody; spheroids; tumor targeting; biodistribution
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MDPI and ACS Style

Collado Camps, E.; van Lith, S.A.M.; Frielink, C.; Lankhof, J.; Dijkgraaf, I.; Gotthardt, M.; Brock, R. CPPs to the Test: Effects on Binding, Uptake and Biodistribution of a Tumor Targeting Nanobody. Pharmaceuticals 2021, 14, 602. https://doi.org/10.3390/ph14070602

AMA Style

Collado Camps E, van Lith SAM, Frielink C, Lankhof J, Dijkgraaf I, Gotthardt M, Brock R. CPPs to the Test: Effects on Binding, Uptake and Biodistribution of a Tumor Targeting Nanobody. Pharmaceuticals. 2021; 14(7):602. https://doi.org/10.3390/ph14070602

Chicago/Turabian Style

Collado Camps, Estel, Sanne A.M. van Lith, Cathelijne Frielink, Jordi Lankhof, Ingrid Dijkgraaf, Martin Gotthardt, and Roland Brock. 2021. "CPPs to the Test: Effects on Binding, Uptake and Biodistribution of a Tumor Targeting Nanobody" Pharmaceuticals 14, no. 7: 602. https://doi.org/10.3390/ph14070602

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