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Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11454-11459. doi: 10.1073/pnas.1812938115. Epub 2018 Oct 22.

Self-assembling supramolecular dendrimer nanosystem for PET imaging of tumors.

Author information

1
Aix-Marseille University, INSERM, INRA, Center de Recherche en Cardiovasculaire et Nutrition (C2VN), 13385 Marseille, France.
2
Aix-Marseille University, Centre Européen de Recherche en Imagerie Médicale (CERIMED), 13005 Marseille, France.
3
Aix-Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France.
4
Aix-Marseille University, CNRS, Institut de Chimie Radicalaire (ICR), 13013 Marseille, France.
5
Molecular Biology and Nanotechnology Laboratory, Department of Engineering and Architecture, University of Trieste, 34127 Trieste, Italy.
6
Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, Beijing 100081, China.
7
School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
8
School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
9
Aix-Marseille University, CNRS, INSERM, Institut Paoli-Calmettes, Centre de Recherche en Cancériologie de Marseille (CRCM), 13273 Marseille, France.
10
Aix-Marseille University, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France; ling.peng@univ-amu.fr.

Abstract

Bioimaging plays an important role in cancer diagnosis and treatment. However, imaging sensitivity and specificity still constitute key challenges. Nanotechnology-based imaging is particularly promising for overcoming these limitations because nanosized imaging agents can specifically home in on tumors via the "enhanced permeation and retention" (EPR) effect, thus resulting in enhanced imaging sensitivity and specificity. Here, we report an original nanosystem for positron emission tomography (PET) imaging based on an amphiphilic dendrimer, which bears multiple PET reporting units at the terminals. This dendrimer is able to self-assemble into small and uniform nanomicelles, which accumulate in tumors for effective PET imaging. Benefiting from the combined dendrimeric multivalence and EPR-mediated passive tumor targeting, this nanosystem demonstrates superior imaging sensitivity and specificity, with up to 14-fold increased PET signal ratios compared with the clinical gold reference 2-fluorodeoxyglucose ([18F]FDG). Most importantly, this dendrimer system can detect imaging-refractory low-glucose-uptake tumors that are otherwise undetectable using [18F]FDG. In addition, it is endowed with an excellent safety profile and favorable pharmacokinetics for PET imaging. Consequently, this dendrimer nanosystem constitutes an effective and promising approach for cancer imaging. Our study also demonstrates that nanotechnology based on self-assembling dendrimers provides a fresh perspective for biomedical imaging and cancer diagnosis.

KEYWORDS:

EPR effect; bioimaging; dendrimer; supramolecular nanomicelle; tumor diagnosis

PMID:
30348798
PMCID:
PMC6233080
DOI:
10.1073/pnas.1812938115
[Indexed for MEDLINE]
Free PMC Article

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