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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 125 I through a facile standard Iodo-Gen method. The resulting [ 125 I]RGD-CR780-PEG5K NPs showed effective accumulation in α v β 3 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 [ 125 I]RGD-CR780-PEG5K NPs allowed thorough tumor ablation and inhibition of tumor relapse at a relatively low laser energy (0.5 W/cm 2 ). Overall, this work offers a proper methodology to fabricate tumor-targeted multi-modal nanotheranostic agents, providing great opportunity for precision imaging and cancer therapy.

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