Iodine-125-labeled cRGD-gold nanoparticles as tumor-targeted radiosensitizer and imaging agent

Research interests on radiosensitive property of gold nanoparticles (GNPs) are rapidly raised because of the extensively proved in vitro effectiveness and clinical necessity. However, the issue of targeted accumulation of GNPs in tumor tissues hindered the transference to in vivo applications. In this study, hybrid nano-sized cyclic Arg-Gly-Asp-conjugated GNPs (cRGD-GNPs) integrated with radioactive iodine-125 was fabricated as tumor-targeted radiosensitizer. Therapeutic effects, including acute apoptosis (2 days post treatment) and long-term influence (up to 21 days), were investigated on NCI-H446 tumor-bearing mice via Tc-99 m-Annexin V SPECT and volume measurements, respectively. Apoptosis and volume loss were consistent in showing that tumor growth was effectively suppressed via the treatment of (125)I-cRGD-GNP sensitized radiotherapy (RT), a more significantly radiosensitive effect than the treatment of non-targeted GNPs with RT, RT treatment alone, and no treatment. SPECT/CT images showed that the uptake of cRGD-GNPs by tumor tissues reached the peak target/non-target value of 4.76 at around 2 h post injection, and dynamic radioactivity monitoring showed that (125)I-cRGD-GNPs maintained about 2.5% of injected dosage at 55 h post injection. For long-term influence, a significant radiosensitized RT-induced volume loss was observed. Hence, cyclic RGD conjugation makes the GNP-based radiosensitizer tumor targeting, offering a new modality for enhancing radiotherapeutic efficacy. Additionally, the introduction of I-125 serves as both a therapeutic factor and a radiotracer for in vivo tracking of GNPs.