Single-Molecule Dendritic Mri Nanoprobes Reveal the Size-Dependent Tumor Entrance.

The 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, we designed 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. We found that the r 1 relaxivity and MR imaging signals increased with the nanoparticle size. The nanoprobe with a lower limit of critical size threshold around ∼8.0 nm achieved superior tumor accumulation and penetration. These single-molecule MRI nanoprobes can be served to precisely examine the size-related nanoparticle-biological interactions. This article is protected by copyright. All rights reserved.