188Re-labeled hyperbranched polysulfonamine as a robust tool for targeted cancer diagnosis and radioimmunotherapy

Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the functionalization of HPSA, both N -succinimidyl 3-(2-pyridyldithio) propionate (SPDP) for tethering the human-mouse chimeric monoclonal antibody CH12 and N -hydroxy succinimidyl S -acetylmercaptoacetyltriglycinate (NHS-MAG 3 ) for labeling 188 Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages, attaining the SPDP-HPSA-MAG 3 intermediate. In order to reserve the structural integrity of CH12, the fragment crystallizable (Fc) region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N -( κ -maleimidoundecanoic acid) hydrazide (KMUH). After chelating 188 Re with MAG 3 group, the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region. As a result, both the epidermal growth factor receptor vIII (EGFRvIII) targeted monoclonal antibody CH12 and the radionuclide 188 Re were conjugated to the HPSA-based vehicles, forming the 188 Re-labeled and CH12-tethered HPSA (CH12-HPSA- 188 Re). The molecular weight and in vitro stability of CH12-HPSA- 188 Re were evaluated by gel electrophoresis and paper chromatography. On one hand, the CH12-HPSA- 188 Re could specifically bind to the EGFRvIII-positive human hepatocarcinoma cells in vitro . On the other hand, it could also target at the tumor tissue of nude mice in vivo . Hence, the CH12-HPSA- 188 Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.