Radiolabeled Angiogenesis-Targeting Croconaine Nanoparticles for Trimodality Imaging Guided Photothermal Therapy of Glioma.

To meet the criteria of effective theranostics, biocompatible nanomedicine endowing intrinsic therapeutic and imaging properties have gained extraordinary momentum. In this study, an ultra-stable near-infrared (NIR) dye croconaine (CR780) was engineered with arginine-glycine-aspartic acid (RGD) peptide and polyethylene glycol (PEG), which was then self-assembled into uniform nanoparticles (NPs). These RGD-CR780-PEG5K assemblies were radiolabeled with 125I through a facile standard Iodo-Gen method. The resulting [125I]RGD-CR780-PEG5K NPs showed effective accumulation in αvβ3 integrin expressing glioblastoma, as evidenced by single photon emission computed tomography (SPECT)/CT and NIR fluorescence imaging. More importantly, high-resolution photoacoustic imaging revealed that these NPs selectively targeted to angiogenic tumor vessels. With the favorable tumor selective accumulation and high photothermal conversion efficiency, the [125I]RGD-CR780-PEG5K NPs allowed thorough tumor ablation and inhibition of tumor relapse at a relatively low laser energy (0.5 W/cm2). Overall, this work offers a proper methodology to fabricate tumor-targeted multi-modal nanotheranostic agents, providing great opportunity for precision imaging and cancer therapy.