Fibronectin extra-domain B-recognizing gold nanoparticles as an innovative tool for neuroblastoma targeting

Background/Objectives: Neuroblastoma (NB) is the most common extracranial solid tumor in children and accounts for 12-15% of pediatric cancer-related deaths. Current multimodal therapies still lack of specific cellular targets, causing systemic toxicity and drug resistance. The development of innovative tumor-targeted nanoformulations might represent a promising approach to enhance NB diagnosis and antitumor efficacy, while decreasing off targets side effects. Fibronectin extra-domain B (FN-EDB) is upregulated in the tumor microenvironment. Methods: Here, FN-EDB expression was evaluated by immunohistochemical (IHC) staining in several animal models of NB. A gold nanoparticle, decorated with an antibody (Ab) recognizing FN-EDB (L19-AuNP) was developed by the company Nano Flow and its tumor binding was tested by ELISA in vitro and in Patient-Derived Xenografts (PDX) models of NB by photoacoustic imaging in vivo . Results: All models of NB used expressed FN-EDB, at the tumor cell, stroma and tumor vasculature levels. Compared to the non-targeted (no L19 Ab) Au-NP (size: 35.59 ± 2.54 nm; PDI: 0.47 ± 0.08; zeta potential: -51.18 ± 0.84), L19-AuNP was found to be stable (size: 108.70 ± 1.37 nm; PDI: 0.29 ± 0.07; zeta potential: -28.34 ± 0.48) and able to specifically bind to FN-EDB in vitro . In vivo , L19-AuNP specifically homed into PDX of NB, accumulating more in the tumor expressing higher levels of FN-EDB. Conclusions: In this preliminary study, L19-AuNP was shown to be a novel diagnostic tool specific for binding NB expressing FN-EDB, paving the way for the development of theranostic nanoformulations co-encapsulating gold moiety and standard-of-care for NB.