Quantitative Detection of In Vivo Aggregation Degree for Enhanced M2 Macrophage MR Imaging.

In situ self-assembly in vivo can be used in the enhanced diagnosis and therapy of major diseases such as cancer and bacterial infections on the basis of an assembly/aggregation-induced-retention (AIR) effect. However, the aggregation degree (α agg ) is a significant parameter for determining the delivery efficiency to lesions in a complex physiological environment and a real-time quantitative calculation of the aggregation degree in vivo is still a great challenge. Here, we developed a magnetic resonance imaging (MRI) method for sensitive and quantitative calculation of α agg with a detection limit of 10 -4 M and a bioactivated in vivo assembly (BIVA) magnetic resonance (MR) probe was optimized for enhanced T 1 -weighted MR imaging of M2 macrophages in tumors. Our MRI quantitative calculation method had a high fitting degree ( R 2 = 0.987) with the gold standard fluorescence (FL) method. On the basis of the BIVA mechanism of CD206 active targeting and cathepsin B specific tailoring to induce an in situ nanofiber assembly, our optimized BIVA probe exhibited a high intracellular aggregation degree of over 70% and a high in vivo α agg value of over 55%. Finally, the aggregation-enhanced T 1 MR signal and the AIR effect both contributed to enhanced T 1 -weighted MR imaging of M2 macrophages in triple-negative breast cancer. We believe that our α agg real-time quantitative calculation method of MRI will help to further screen and optimize the in vivo enhanced imaging and treatment of the BIVA drug.