Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
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Active targeting and in vivo multimodal imaging of renally excretable polymer nanoparticlesPant, K.; Zarschler, K.; Neuber, C.; Pufe, J.; Pietzsch, J.; Steinbach, J.; Stephan, H.; Haag, R.
Multimodal imaging represents a strategy to integrate multiple modalities on a single carrier molecule so as to increase the detection sensitivity and to obviate the need to administer compounds with different pharmacokinetics. In this regard, dendritic polyglycerols are highly biocompatible nanoscale scaffolds with multiple attachment sites, anti-fouling properties and small size (2-20 nm).1 The great versatility of the dendritic polyglycerols allows to fine tune physicochemical parameters such as the size, water solubility, surface charge that are relevant for the successful preparation of theranostic systems. Previous experiments showed that the dendritic polyglycerols (>10kDa) show a fast renal clearance with negligible uptake in the mononuclear phagocytic system (MPS) organs such as the liver and spleen.2-3 The purpose of this work to design a PET/OI dual modal construct based on dendritic polyglycerols for epidermal growth factor receptor (EGFR) targeting. In this regard, a one-pot strategy was employed for simultaneous attachment of fluorescent labels for optical imaging (cy3/cy7) and macrocyclic chelators based on a 1,4,7-triazacyclononane system for 64Cu (PET tracer) to thiol anchoring groups of the dPGs. A small camelid single-domain antibody (sdAb) representing a potential recognition agent for EGFR as targeting vector was attached (1). In parallel, a probe with similar surface characteristics but an EGFR unspecific sdAb (control) was synthesized (2). The conjugates were purified using affinity chromatography, which selectively separates the antibody-conjugated mul-timodal conjugates. In vitro and in vivo studies were conducted to assess its diagnostic potential. The in vitro results revealed a highly specific receptor mediate uptake of 1 in EGFR expressing A431 and FaDu cell lines using confocal microscopy and radio detection.
Intravenous injection of 1 and 2 on mouse xenografted models studies using PET and optical imaging revealed an overwhelming tumor accumulation of the EGFR-specific 1 in comparison to the EGFR-unspecific 2 and a minimum off-target accumulation of both conjugates. These results unveil the potential of dendritic polyglycerols as efficient multimodal platforms for theranostic applications.
Keywords: dendritic polyglycerols, cancer, biodistribution, radiolabeling, renal clearance, protein corona, biomedical applications.
Nanotech France 2017, 28.-30.06.2017, PARIS, France