Figure 5: The cargo obstructs the access of water in the nanophores’ proximity.

(a) Schematic representation of the proposed model that suggests that the presence of cargo within the coating of IONP hinders the diffusion of water molecules, concomitantly affecting the ability of nanoparticles to efficiently dephase water’s protons. At high D₂O concentrations, the changes on (b) T2 and (c) T1 were abrogated (mean±s.e.m., n=3), suggesting that the observed increases in T2 and T1 during cargo loading occurred upon blockage of water molecules by the entrapped cargo ([Fe]_PAA-IONP=2.5 μg ml⁻¹) rather than an effect exerted by the payload. (d–f) Diffusion-weighted MRI revealed that the presence of molecular payload within Ferumoxytol’s coating affected the diffusion of water molecules ([Fe]_Ferumoxytol=5 μg ml⁻¹ for all wells; mean±s.e.m., n=6). The cargo’s effect on ADC correlated with the observed changes in T2 and T1 signal (mean±s.e.m., n=6; linear regression correlation coefficients r_T2=0.95 and r_T1=0.92; vehicle: unloaded nanoparticles; mean±s.e.).