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

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 2 ) 2 ) 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, p < 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. Keywords: gastric cancer, lymph node mapping, lymphatic vessels, polydopamine-based nanoparticles, systemic lymphadenectomy