Quantitative Detection of <i>In Vivo</i> Aggregation Degree for Enhanced M2 Macrophage MR Imaging.

Abstract

<i>In situ</i> self-assembly <i>in vivo</i> 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 <i>in vivo</i> 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 <i>in vivo</i> assembly (BIVA) magnetic resonance (MR) probe was optimized for enhanced <i>T</i>₁-weighted MR imaging of M2 macrophages in tumors. Our MRI quantitative calculation method had a high fitting degree (<i>R</i>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 <i>in situ</i> nanofiber assembly, our optimized BIVA probe exhibited a high intracellular aggregation degree of over 70% and a high <i>in vivo</i> α_agg value of over 55%. Finally, the aggregation-enhanced <i>T</i>₁ MR signal and the AIR effect both contributed to enhanced <i>T</i>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 <i>in vivo</i> enhanced imaging and treatment of the BIVA drug.