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

Ning Su,Guangli Liang,Yajie Dang,Guizhi Liu

doi:10.1186/s11671-015-0864-9

Abstract

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 125I-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 125I-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.

Highlights

Surface plasmon resonance and the ability to bind thiol and amine group enabled the biological and medical applications of gold nanoparticles (GNPs) [1], such as photodynamic therapy [2], therapeutic delivery agents [3], diagnostic agents [4,5], and radiosensitizer [6,7]
dynamic light scattering (DLS) hydrodynamic diameter of polyethylene glycol (PEG)-covered GNPs was 45.2 ± 2.6 nm. cRGD was successfully conjugated to GNPs based on the changes of surface ζ potential and RGD concentration changes of reaction supernate reflected by the UV spectrum
Attributing to the PEGs covering and cyclic RGD conjugation, cRGD-GNPs targeted tumor more efficiently and avoided heavy capture by the liver, while part of the nanoparticles were still absorbed by the gallbladder. cRGD-GNPs were expelled from the blood system rapidly and targeted tumor with a peak value of T/NT of 4.76 at 2 h post injection

Summary

Introduction

Surface plasmon resonance and the ability to bind thiol and amine group enabled the biological and medical applications of gold nanoparticles (GNPs) [1], such as photodynamic therapy [2], therapeutic delivery agents [3], diagnostic agents [4,5], and radiosensitizer [6,7]. Dose enhancement factor (DEF) related to radiosensitive effect ranges from 1.01 to 2.11 [8], depending on various items, such as the dosage of radiation, concentration, size, morphology, surface coating, and charging of radiosensitizer. Size and morphology influence the cellular uptake and cytotoxicity. The uptake of shorter rod-shaped GNPs is higher than that of longer ones, but both are lower than spherical ones [13]. Besides EPR effect, reticuloendothelial system (RES) heavily influences the in vivo distribution of nano-sized radiosensitizer. Polyethylene glycol (PEG) coating is effective to reduce the RES uptake and

Methods

Results

Conclusion