Multimodal Imaging By Polydopamine Nanoparticles for Effective Pre- and Intra-Operative Lymph-Node Screening in Gastric Cancer Using Mice Model.

Abstract

INTRODUCTION: Systematic lymphadenectomy is crucial in gastric cancer surgery for improving patient prognosis. However, current clinical lymph node (LN) mapping relies on fragmentary single-modal imaging agents, which suffer from low accuracy in N-staging and lack integration between preoperative and intraoperative visualization. METHODS: We developed polydopamine-based nanoparticles (PEG-PDA@IR820/Gd(NH)) termed PPIG NPs) as a unified multimodal imaging agent for magnetic resonance (MR), optical, near-infrared (NIR) fluorescence, and thermal LN mapping. PPIG NPs were synthesized in three distinct size ranges (50-100 nm, 100-150 nm, 150-200 nm). Their imaging performance and lymphatic drainage kinetics were evaluated in vivo in a mouse model. Furthermore, the efficacy of PPIG NPs for LN identification was validated in fresh human gastric and colon cancer specimens via subserosal injection. RESULTS: The differently sized PPIG NPs exhibited tunable and size-dependent lymphatic drainage and retention. In mice, they enabled integrative pre-operative (MR) and intra-operative (optical/NIR fluorescence/thermal) multimodal mapping of popliteal LNs. In human specimens, PPIG NPs specifically delineated lymphatic vessels and LNs. Guided by this dual-modal (optical/NIR) mapping, lymphadenectomy in human gastric specimens achieved a significantly higher LN yield compared to conventional visual inspection (mean number: 55.4 vs 36.8,< 0.05). The approach also facilitated the precise identification of residual lymphatic vessels post-dissection. CONCLUSION: PPIG NPs provide an integrative pre- and intra-operative multimodal LN mapping platform. This strategy, enabling "see-before-cut" planning and "trace-while-cutting" navigation, demonstrates superior accuracy for LN and lymphatic vessel identification compared to current fragmentary techniques, showing promising potential for guiding precise lymphadenectomy in gastric cancer.