Radiosensitizer-Releasing Fiducial ‘Nanofiducial’: A New Concept in Radiotherapy

Abstract

Fiducial is a material used in stereotactic radiotherapy (SRT). Additionally, radiosensitizing nanostructures are an interesting opportunity for improving RT clinical benefits. In this study, it was aimed to combine both technologies by designing and synthesizing a tailor-made 'nanofiducial' functionalized with a radiosensitizing nanoparticle. AGuIX are sub-5 nm nanoparticles containing gadolinium (Z = 64) having both MRI contrast capability and radiosensitization effects. It was planned to embed the AGuIX nanoparticle in poly(lactic-co-glycolic acid) (PLGA) nanofiber mats. Nanofiber mats were prepared by electrospinning method. Imaging of the nanofiber structure was evaluated using Scanning Electron Microscopy (SEM). Detailed analyzes were carried out for porosity and mechanical strength measurements in addition to DSC and FTIR. EDS micrographs of fiber meshes were taken to show that AGuIX was loaded into nanofiber mats. The amount of AGuIX released from the nanofiber mats in PBS was quantified by inductively coupled plasma mass spectrometry (ICP-MS). Nanofibers were produced in two different forms, one 'no AguIX' embedded and the other loaded with '5 % AguIX'. The nanofiber formulation was prepared using PLGA poly(lactic-co-glycolic acid) 50:50 polymer with a molecular weight of 38,000-54,000. A mixture of Tethrahydrofuran and Dimethylformamide was used as the polymer solvent. The mixing ratio of THF:DMF was 65:35 and the rate of PLGA was 25%. According to the SEM results, nanofibers were randomly aligned and the release of AGuIX was observed up to 12 hours after fiducial formation in pH 7.4 PBS buffer solution. Nanofiducials computed tomography images were taken and nanofiducials were viewed as hypointense area. Hounsfield Unit values for "no AGuIX" sample and "5% AGuIX containing sample" were as follows: average -62.5(max -16; STD 11.7); -87.2 (max -60; STD 8.7). Radiosensitizing nanostructures are promising for increasing the effectiveness of radiotherapy in cancer treatment, achieving high dose effects at lower doses, and reducing side effects. In this study, a fiducial structure functionalized with an effective radiosensitizing nanoparticle was preliminary tested for local application.