Baselga Marta, Güemes Antonio, Yus Cristina, Alejo Teresa, Sebastián Víctor, Arribas Dolores, Mendoza Gracia, Monleón Eva, Arruebo Manuel
Institute for Health Research Aragon (IIS Aragón), 50009 Zaragoza, Spain.
Department of Surgery, University of Zaragoza, 50009 Zaragoza, Spain.
Nanomaterials (Basel). 2024 Jul 4;14(13):1149. doi: 10.3390/nano14131149.
In breast cancer, Targeted Axillary Dissection (TAD) allows for the selective excision of the sentinel lymph node (SLN) during primary tumor surgery. TAD consists of the resection of labelled SLNs prior to neoadjuvant chemotherapy (NACT). Numerous clinical and preclinical studies have explored the use of carbon-based colloids for SLN tattooing prior to NACT. However, carbon vectors show varying degrees of inflammatory reactions and, in about one fifth of cases, carbon particles migrate via the lymphatic pathway to other nodes, causing the SLN to mismatch the tattooed node. To overcome these limitations, in this study, we explored the use of melanin as a staining endogenous pigment. We synthesized and characterized melanin-loaded polymeric nanoparticles (Mel-NPs) and used them to tattoo lymph nodes in pig animal models given the similarity in the size of the human and pig nodes. Mel-NPs tattooed lymph nodes showed high identification rates, reaching 83.3% positive identification 16 weeks after tattooing. We did not observe any reduction in the identification as time increased, implying that the colloid is stable in the lymph node tissue. In addition, we performed histological and ultrastructural studies to characterize the biological behavior of the tag. We observed foreign-body-like granulomatous inflammatory responses associated with Mel-NPs, characterized by the formation of multinucleated giant cells. In addition, electron microscopy studies showed that uptake is mainly performed by macrophages, and that macrophages undergo cellular damage associated with particle uptake.
在乳腺癌中，靶向腋窝淋巴结清扫术（TAD）可在原发性肿瘤手术期间选择性切除前哨淋巴结（SLN）。TAD包括在新辅助化疗（NACT）之前切除标记的SLN。许多临床和临床前研究都探讨了在NACT之前使用碳基胶体进行SLN纹身的情况。然而，碳载体显示出不同程度的炎症反应，并且在约五分之一的病例中，碳颗粒通过淋巴途径迁移到其他淋巴结，导致SLN与纹身淋巴结不匹配。为了克服这些局限性，在本研究中，我们探索了使用黑色素作为内源性染色色素。我们合成并表征了负载黑色素的聚合物纳米颗粒（Mel-NPs），并鉴于人和猪淋巴结大小相似，将其用于猪动物模型的淋巴结纹身。Mel-NPs纹身的淋巴结显示出高识别率，纹身后16周阳性识别率达到83.3%。我们没有观察到随着时间增加识别率有任何降低，这意味着该胶体在淋巴结组织中是稳定的。此外，我们进行了组织学和超微结构研究以表征标记物的生物学行为。我们观察到与Mel-NPs相关的异物样肉芽肿性炎症反应，其特征是形成多核巨细胞。此外，电子显微镜研究表明摄取主要由巨噬细胞进行，并且巨噬细胞在摄取颗粒时会发生细胞损伤。
