Geometrical confinement directed albumin-based nanoprobes as enhanced T₁ contrast agents for tumor imaging

There is an urgent demand for the development of new magnetic resonance imaging (MRI) contrast agents (CAs) with high T₁ contrast ability and good biocompatibility. Herein, we report a novel albumin-based nanoprobe loaded with ibuprofen-modified gadolinium chelates, named Ibu-Gd-BSA nanoparticles (NPs). The interfacial pore structure among the albumin molecules endows the Ibu-Gd-BSA NPs with geometrical confinement, which could prolong the rotational correlation time (τ_R) of CAs and the diffusion correlation time (τ_D) of water molecules trapped within the pores. As a result, the Ibu-Gd-BSA NPs exhibited an extremely high relaxivity of 48.9 mM^-1 s^-1, which is about 9 times higher than that of the clinical contrast agent Gd-DOTA (Dotarem®). In addition, the Ibu-Gd-BSA NPs showed good biocompatibility in vitro and in vivo due to the intrinsically biocompatible property of each component. Moreover, the Ibu-Gd-BSA NPs showed much longer blood circulation half-life and higher accumulation in tumors due to the enhanced permeability and retention effect compared to small molecular CAs. In vivo T₁-weighted MR imaging confirmed that Ibu-Gd-BSA NPs could serve as an optimal candidate for sensitive tumor imaging. This study provides a facile strategy to assemble geometrically confined albumin-based nanoparticles as T₁ CAs with high biocompatibility and enhanced contrast ability, which have great potential for diverse uses in biomedical imaging and disease detection.