Citation: Nan Li, Yue Jin, Li-zhe Xue, Pei-yong Li, De-yue Yan, Xin-yuan Zhu. 188Re-LABELED HYPERBRANCHED POLYSULFONAMINE AS A ROBUST TOOL FOR TARGETED CANCER DIAGNOSIS AND RADIOIMMUNOTHERAPY[J]. Chinese Journal of Polymer Science, ;2013, 31(3): 530-540. doi: 10.1007/s10118-013-1242-7 shu

188Re-LABELED HYPERBRANCHED POLYSULFONAMINE AS A ROBUST TOOL FOR TARGETED CANCER DIAGNOSIS AND RADIOIMMUNOTHERAPY

Received Date: 23 August 2012
Revised Date: 5 October 2012

Fund Project: The work was financially supported by the National Natural Science Foundation of China (Nos. 20974062, 30700175), National Basic Research Program (Nos. 2009CB930400, 2012CB821500), and China National Funds for Distinguished Young Scientists (No. 21025417).

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-MAG3) for labeling 188Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages, attaining the SPDP-HPSA-MAG3 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-(-maleimidoundecanoic acid) hydrazide (KMUH). After chelating 188Re with MAG3 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 188Re were conjugated to the HPSA-based vehicles, forming the 188Re-labeled and CH12-tethered HPSA (CH12-HPSA-188Re). The molecular weight and in vitro stability of CH12-HPSA-188Re were evaluated by gel electrophoresis and paper chromatography. On one hand, the CH12-HPSA-188Re 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-188Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.
- Hyperbranched polymer
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