A self-assembling amphiphilic dendrimer nanotracer for SPECT imaging

Abstract

An amphiphilic dendrimer bearing SPECT imaging reporters is self-assembled into supramolecular nanomicelles for effective tumor imaging.

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

“…Previously, we also supported the synthesis of the dendrimer In‐1 carrying the DOTA cages through isothermal titration calorimetry (ITC). [ 14 ] We used the same approach to study the thermodynamics of the interaction between In 3+ and the dendrimer 2 bearing the NOTA cages for generating In‐2 (Figure 2B). The titration of both dendrimers 1 and 2 with the trivalent cation In 3+ presented very similar calorimetric behaviors.…”

“…To further confirm the spontaneous self‐assembly of In‐1 and In‐2 into nanomicelles, we performed molecular dynamics simulations following a consolidated procedure. [ 13,14 ] Starting from randomly distributed monomers, we obtained stable spherical micelles for both systems during the timescale of the simulations (1.0 µs) (Figure 3D,F,I,J). The corresponding average micelle diameters computed from the equilibrated molecular dynamics simulations were 15 and 13 nm for the In‐1 and In‐2 systems, respectively, which were in good agreement with the experimental results obtained using both dynamic light scattering and transmission electron microscopy.…”

“…By inspecting the conformational structures of both micelles, no back‐folding of the terminal groups was detected, in line with our previous findings obtained for similar systems. [ 13,14 ] Accordingly, the In 3+ ‐bearing terminal units are all located at the periphery of the micelles in both the In‐1 and In‐2 systems. Further analysis of the electrostatic surface potential confirmed the foreseen effect of replacing the DOTA cage with the NOTA scaffold, with a negative electrostatic potential observed for In‐1 (Figure 3I) and a positive potential for In‐2 (Figure 3D), in agreement with the experimentally determined surface zeta potentials (Figure 3C,H).…”

“…[ 7–12 ] We have recently established small amphiphilic dendrimers that are able to self‐assemble into supramolecular nanosystems for effective tumor imaging using positron emission tomography (PET) and single photon emission computed tomography (SPECT) ( Figure ). [ 13,14 ] Both PET and SPECT are radio‐imaging techniques that have a high sensitivity yet unlimited tissue penetration, and are able to visualize functional information quantitatively. [ 15,16 ] Notably, SPECT is the most prevalent clinical imaging modality, accounting for > 75% of all nuclear imaging procedures.…”

“…We previously developed an amphiphilic dendrimer In‐1 composed of a long hydrophobic alkyl chain and a hydrophilic poly(amidoamine) dendron bearing the SPECT radionuclide 111 In(III) complexed with the macrocycle DOTA (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) ring in the chelator DOTAGA (1,4,7,10‐tetraazacyclododececane‐1‐(glutaric acid)‐4,7,10‐triacetic acid) at the terminals ( In‐1 in Figure 1). [ 14 ] By virtue of its amphiphilic nature, In‐1 self‐assembled into small and stable supramolecular nanomicelles for effective SPECT imaging of tumors based on the favorable combination of EPR‐based passive tumor targeting and the dendrimeric structure bearing multivalent SPECT reporters. Nevertheless, In‐1 also displayed high liver retention, which represents a severe limitation for its future clinical translation.…”