Developing an Advanced Nanotracer for Real- Time Surgical Navigation

Abstract

Accurate sentinel lymph node (SLN) identification is essential in image-guided cancer surgery, where tracers must provide efficient lymphatic migration, sufficient nodal retention and real-time intraoperative detectability. However, small molecular dyes such as indocyanine green (ICG) can diffuse rapidly through the lymphatic system, limiting retention in the first draining node. Aimed at enhancing both sensitivity and accuracy in the optical detection of SLN during surgical navigation, human serum albumin (HSA) nanoparticles have been explored as intermediate-size carriers to improve local retention of ICG, while D-mannose functionalization was introduced as a preliminary strategy to promote interactions with mannose receptor-expressing macrophages in lymph nodes. ICG-loaded HSA nanoparticles were therefore developed as preliminary dual optical/single-photon emission computed tomography (SPECT) nanotracers for surgical navigation. Four formulations were prepared to evaluate the influence of crosslinking within the protein network and D-mannose functionalization on the physicochemical properties of the tracer. Crosslinking was identified as the main factor controlling colloidal robustness, producing more homogeneous, reproducible and stable nanoparticles than the non-crosslinked systems. Crosslinked nanoparticles yielded the most balanced radiochemical purity (≥ 95%) without compromising their co loidal stability. Mannose functionalization was achieved, although with poor yields. Overall, crosslinked ICG⊂HSA nanoparticles represent a promising intermediate-size platform for further development as dual nearinfrared (NIR) fluorescence/SPECT imaging tracers for imageguided surgical applications