Selective sentinel lymph node biopsy (SNLB) is the standard method for detecting regional metastases in breast cancer patients. Identifying affected axillary lymph nodes before neoadjuvant treatment is crucial, as such treatment may alter drainage pathways and lymph node morphology, hindering the identification of sentinel lymph nodes. The use of carbon-based tattooing on sentinel lymph nodes (SLN) has been employed as a permanent tattooing method in clinical studies of Targeted Axillary Dissection (TAD), aiding in the SLN identification during surgery. Our study introduces a new method of lymph node tattooing based on poly lactic-co-glycolic (PLGA) particles with encapsulated carbon. This strategy substantially improves tattooing efficiency over single carbon suspensions currently used in clinical studies. We synthesized and characterized carbon-loaded PLGA micro- and nanoparticles, experimentally assessing their biological impact on porcine lymph nodes. The effect of particles' size and concentration was evaluated over time (from 1 to 16 weeks). Light and electron microscopy studies were conducted to characterize the cellular effects induced by the presence of these particles. Our findings reveal that the diverse physicochemical parameters of the particles interact differently with the lymphatic tissue, influencing their biodistribution within the lymph nodes and the intensity of the inflammatory response.