L19-Conjugated Gold Nanoparticles for the Specific Targeting of EDB-Containing Fibronectin in Neuroblastoma

TL;DR

This study explores gold nanoparticles decorated with an antibody that specifically targets a protein found in neuroblastoma tumors, offering a potential new diagnostic and therapeutic tool.

Contribution

The development of L19-conjugated gold nanoparticles for targeting fibronectin extra-domain B in neuroblastoma is novel.

Findings

L19-AuNP specifically binds to fibronectin extra-domain B in neuroblastoma tumor models.

L19-AuNP accumulates in tumors with higher fibronectin extra-domain B levels and shows minimal distribution to healthy organs.

L19-AuNP is more stable than non-functionalized gold nanoparticles, making it suitable for in vivo studies.

Abstract

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 lack 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: FN-EDB expression was evaluated by immunohistochemical staining in cell line-derived and tumor patient-derived 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 xenograft (PDX) models of NB by photoacoustic imaging in vivo. Results: All animal models of NB used have been shown to express FN-EDB. L19 Ab demonstrated excellent binding specificity to FN-EDB both when used in free form and after conjugation to AuNP. Compared to the non-functionalized (no Ab L19-coupled) AuNP, which showed an increase in PDI and zeta potential over time, making them unsuitable for use in in vivo studies, L19-AuNP demonstrated good stability. In vivo, L19-AuNP specifically homed into PDX models of NB, accumulating better in tumors expressing higher levels of FN-EDB. Negligible distribution to healthy organs occurred. Conclusions: In this preliminary study, L19-AuNP was shown to be a novel diagnostic tool specifically for binding NB expressing FN-EDB, paving the way for the development of theranostic nanoformulations co-encapsulating gold moiety and standard-of-care therapy for NB.

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