Boronic acid group modified Mn-porphyrin nanoparticles evade macrophage uptake for lymph node metastasis diagnosis via MRI.

Lymph node metastasis is a crucial factor in cancer prognosis; however, no clinically approved contrast agents are available for its accurate detection via medical imaging. The contribution of macrophage uptake to nanoparticle (NP) accumulation during lymphatic drainage has been a subject of ongoing debate. Herein, we report a novel lymph node imaging strategy designed to enhance lymph node retention while evading macrophage clearance through nanoprobe surface modification, thereby improving the diagnostic accuracy of lymph node metastases. We engineered a series of Pluronic F127-based NPs as magnetic resonance imaging (MRI) contrast agents, incorporating manganese (Mn) porphyrin molecules bearing varied functional groups (-CH3, -OH, -COOH, -NH2, and -B(OH)2). The influence of these surface modifications on physicochemical properties and macrophage-evading capabilities was investigated. Notably, boronic acid-functionalized Mn-porphyrin NPs exhibited exceptional macrophage evasion, demonstrating significantly reduced macrophage uptake in vitro and prolonged blood circulation in vivo relative to NPs modified with alternative functional groups. In a lymph node metastasis model, boronic acid-modified Mn-porphyrin NPs administered via local footpad injection (0.005 mmol Mn/kg) achieved optimal lymph node MRI contrast with an extended imaging window. Furthermore, in New Zealand rabbits, even at lower doses (0.0025 mmol Mn/kg), boronic acid-modified Mn-porphyrin NPs provided excellent lymphatic system visualization, highlighting the potential for further translational studies. In summary, this study confirms the feasibility of a boronic acid group modification strategy that evades macrophage uptake and utilizes lymphatic drainage to diagnose lymph node metastasis, offering valuable insights for the development of next-generation macrophage-evading nanoprobes.