Small, but hitting the target – towards novel nanoparticle platforms for diagnostic cancer imaging


Small, but hitting the target – towards novel nanoparticle platforms for diagnostic cancer imaging

Zarschler, K.

For effective localization of functionalized nanoparticles at diseased tissues such as solid tumours or metastases through biorecognition, appropriate targeting vectors directed against selected tumour biomarkers are a key prerequisite. The diversity of such vector molecules ranges from proteins, including antibodies and fragments thereof, through aptamers and glycans to short peptides and small molecules.
The presented work focusses on the epidermal growth factor receptor (EGFR) acting as a model receptor, since it is overexpressed and/or deregulated in a variety of solid tumours. Thus, bioconjugation of EGFR-specific single-domain antibodies (sdAbs) to different nanomaterials and characterization of sdAb-conjugates covering in vitro cancer cell imaging, cell proliferation as well as EGFR phosphorylation and signalling are described. The specificity of the sdAb-conjugates is investigated by way of receptor RNA silencing techniques with increasing complexity in vitro by introducing increasing concentrations of human or bovine serum. The results show that sdAb-functionalised nanomaterials can effectively target the EGFR, even in more complex bovine and human serum conditions where targeting specificity is largely conserved for increasing serum concentration. For highly affine targeting ligands such as sdAbs, targeting a receptor such as EGFR with low serum competitor abundance, receptor recognition function can still be partially realised in complex conditions. Moreover, sdAb-mediated biorecognition of EGFR is not restricted to particular nanomaterials, but was observed to work efficiently in combination with a variety of materials.

  • Lecture (others)
    Eingeladener Vortrag am Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia, 27.11.2014, Melbourne, Australien

Permalink: https://www.hzdr.de/publications/Publ-23619
Publ.-Id: 23619