Surface Charge of Supramolecular Nanosystems for In Vivo Biodistribution: A MicroSPECT/CT Imaging Study

Ling Ding (1) , Zhenbin Lyu (1) , Beatrice Louis (2) , Aura Tintaru (3) , Erik Laurini (4) , Domenico Marson (4) , Mengjie Zhang (5) , Wanxuan Shao (5) , Yifan Jiang (1) , Ahlem Bouhlel (6, 7) , Laure Balasse (7, 6) , Philippe Garrigue (7, 6) , Eric Mas (8) , Suzanne Giorgio (1) , Juan Iovanna (8) , Yuanyu Huang (5) , Sabrina Pricl (4, 9) , Benjamin Guillet (6, 7) , Ling Peng (1)

1 CINaM - Centre Interdisciplinaire de Nanoscience de Marseille
2 INSERM - Institut National de la Santé et de la Recherche Médicale
3 ICR - Institut de Chimie Radicalaire
4 Università degli studi di Trieste = University of Trieste
5 BIT - Beijing Institute of Technology
6 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
7 CERIMED - Centre Européen de Recherche en Imagerie médicale
8 CRCM - Centre de Recherche en Cancérologie de Marseille
9 University of Lódź = Uniwersytet Łódzki

Bioimaging has revolutionized medicine by providing accurate information for disease diagnosis and treatment. Nanotechnology‐based bioimaging is expected to further improve imaging sensitivity and specificity. In this context, supramolecular nanosystems based on self‐assembly of amphiphilic dendrimers for single photon emission computed tomography (SPECT) bioimaging are developed. These dendrimers bear multiple In3+ radionuclides at their terminals as SPECT reporters. By replacing the macrocyclic 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid cage with the smaller 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid scaffold as the In3+ chelator, the corresponding dendrimer exhibits neutral In3+‐complex terminals in place of negatively charged In3+‐complex terminals. This negative‐to‐neutral surface charge alteration completely reverses the zeta‐potential of the nanosystems from negative to positive. As a consequence, the resulting SPECT nanoprobe generates a highly sought‐after biodistribution profile accompanied by a drastically reduced uptake in liver, leading to significantly improved tumor imaging. This finding contrasts with current literature reporting that positively charged nanoparticles have preferential accumulation in the liver. As such, this study provides new perspectives for improving the biodistribution of positively charged nanosystems for biomedical applications.

Domaines: Chimie de coordination; Imagerie

Ling Ding, Zhenbin Lyu, Beatrice Louis, Aura Tintaru, Erik Laurini, et al.. Surface Charge of Supramolecular Nanosystems for In Vivo Biodistribution: A MicroSPECT/CT Imaging Study. Small, 2020, 16, pp.301-304. ⟨10.1002/smll.202003290⟩. ⟨hal-02992689⟩