Multifunctional Molecular Probe Modified With BmK CT Used For The Diagnosis And Treatment Of Gliomas

Gliomas are the most common and fatal tumors in brain,which are difficult to be cured by conventional therapies.¹³¹I-labeled Buthus martensii Karsch chlorotoxin?BmK CT?has been reported to be used for SPECT imaging and radiotherapy of gliomas.Meanwhile,dendrimer-entrapped gold nanoparticles?Au DENPs?are praised to enhance the biocompatibility for computed tomography?CT?imaging.Herein,in this study,we explored the synthesis,characterization,and utilization of ¹³¹I-labeled BmK CT-modified Au DENPs for targeted Single Photon Emission Computed Tomography?SPECT?/CT imaging and radionuclide therapy of gliomas.The dendrimers were prepared using PEG-acetylated amine-terminated poly?amidoamine?dendrimers as a template to conjugate 3-?4'-Hydroxyphenyl?propionic Acid-OSu?HPAO?and entrap gold nanoparticles.The formed Au DENPs were then modified with BmK CT,a glioma-targeting peptide,to enable its binding affinity to glioma cells.The gained Au DENPs-BmK CT before and after ¹³¹I labeling were characterized in vitro and in vivo.The cytotoxicity of Au DENPs-BmK CT was assessed via CCK-8 assay and its binding affinity to C6 glioma cells was evaluated by flow cytometry and confocal microscopy experiment.CT and SPECT imaging in vitro was performed to assess the binding affinity of ¹³¹I-Au DENPs-BmK CT to C6 glioma cells and cell proliferation assay was used to detect its inhibition rate on C6 glioma cells growth.The potential of ¹³¹I-Au DENPs-BmK CT used for SPETCT/CT imaging and targeted radionuclide therapy of gliomas in vivo was also evaluated.The formed nanoprobes were stable and could be completely dissolved in aqueous solution.Cell cytotoxicity assay showed that Au DENPs-BmK CT did not affect C6 glioma cells viability and its specific affinity to C6 glioma cells was proved by flow cytometry and confocal microscopy experiment.¹³¹I-Au DENPs-BmK CT exhibited high radiochemical purity and good stability.CT and SPECT imaging in vitro demonstrated its specific affinity to C6 glioma cells and it displayed obvious inhibitory effect on C6 glioma cells growth.Moreover,¹³¹I-Au DENPs-BmK CT exhibited efficient SPECT/CT imaging performance and therapeutic effect in glioma bearing nude mice.In conclusion,the new designed radiolabeled multifunctional dendrimeric nanoplatform,¹³¹I-Au DENPs-BmK CT,has a great potential to be used for SPECT/CT imaging and targeted radiotherapy of gliomas.