Evaluation of the Active Targeting of Melanin Granules after Intravenous Injection of Dendronized Nanoparticles

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]­Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles...

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Bibliographic Details
Published in:Molecular pharmaceutics 2018-02, Vol.15 (2), p.536-547
Main Authors: Bordeianu, C, Parat, A, Piant, S, Walter, A, Zbaraszczuk-Affolter, C, Meyer, F, Begin-Colin, S, Boutry, S, Muller, R. N, Jouberton, E, Chezal, J.-M, Labeille, B, Cinotti, E, Perrot, J.-L, Miot-Noirault, E, Laurent, S, Felder-Flesch, D
Format: Article
Language:English
Subjects:
Animals
Biopsy
Cancer
Cell Line, Tumor - transplantation
Chemical Sciences
Humans
Injections, Intravenous
Life Sciences
Lutetium - chemistry
Magnetic Resonance Imaging
Male
Melanins - metabolism
Melanoma - diagnostic imaging
Melanoma - pathology
Mice
Microscopy, Confocal
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Polymers - administration & dosage
Polymers - chemistry
Radioisotopes - chemistry
Radionuclide Imaging
Radiopharmaceuticals - administration & dosage
Radiopharmaceuticals - chemistry
Skin - diagnostic imaging
Skin - pathology
Skin Neoplasms - diagnostic imaging
Skin Neoplasms - pathology
Tissue Distribution
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Summary:The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]­Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells’ membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]­Lu-NPs10@D1_ICF_DOTAGA at 2 h post-intravenous injection (pi), and the highest tumor uptake of the control probe [177Lu]­Lu-NPs10@D1_DOTAGA at 30 min pi, probably due to the enhanced permeability and retention effect. In addition, ex vivo confocal microscopy studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.
ISSN:1543-8384
1543-8392
DOI:10.1021/acs.molpharmaceut.7b00904