Single‐Molecule Dendritic MRI Nanoprobes Reveal the Size‐Dependent Tumor Entrance

Abstract

AbstractThe tumor entrance of drug delivery systems, including therapeutic proteins and nanomedicine, plays an essential role in affecting the treatment outcome. Nanoparticle size is a critical but contradictory factor in making a trade‐off among blood circulation, tumor accumulation, and penetration. Here, this work designs a series of single‐molecule gadolinium (Gd)‐based magnetic resonance imaging (MRI) nanoprobes with well‐defined sizes to precisely explore the size‐dependent tumor entrance in vivo. The MRI nanoprobes obtained by divergent synthesis contain a core molecule of macrocyclic Gd(III)‐chelate and different layers of dendritic lysine units, mimicking globular protein. This work finds that the r1 relaxivity and MR imaging signals increase with the nanoparticle size. The nanoprobe with a lower limit of critical size threshold ≈8.0 nm achieves superior tumor accumulation and penetration. These single‐molecule MRI nanoprobes can be served to precisely examine the size‐related nanoparticle‐biological interactions.