Radiation-Responsive Amino Acid Nanosensor Gel (RANG) for Radiotherapy Monitoring and Trauma Care

Abstract

Accurate detection of doses is critical for the development of effective countermeasures and patient stratification strategies in cases of accidental exposure to ionizing radiation. Existing detection devices are limited by high fabrication costs, long processing times, need for sophisticated detection systems, and/or loss of readout signal over time, particularly in complex environments. Here, we describe fundamental studies on amino acid-facilitated templating of gold nanoparticles following exposure to ionizing radiation as a new colorimetric approach for radiation detection. Tryptophan demonstrated spontaneous nanoparticle formation, and parallel screening of a library of amino acids and related compounds led to the identification of lead candidates, including phenylalanine, which demonstrated an increase in absorbance at wavelengths typical of gold nanoparticles in the presence of ionizing radiation (X-rays). Evaluation of screening, i.e., absorbance data, in concert with chemical informatics modeling led to the elucidation of physicochemical properties, particularly polarizable regions and partial charges, that governed nanoparticle formation propensities upon exposure of amino acids to ionizing radiation. NMR spectroscopy revealed key roles of amino and carboxy moieties in determining the nanoparticle formation propensity of phenylalanine, a lead amino acid from the screen. These findings were employed for fabricating radiationresponsive amino acid nanosensor gels (RANGs) based on phenylalanine and tryptophan, and efficacy of RANGs was demonstrated for predicting clinical doses of ionizing radiation in anthropomorphic thorax phantoms and in live canine patients undergoing radiotherapy. The use of biocompatible templating ligands (amino acids), rapid response, simplicity of fabrication, efficacy, ease of operation and detection, and long-lasting readout indicate several advantages of the RANG over existing detection systems for monitoring radiation in clinical radiotherapy, radiological emergencies, and trauma care.

Versatile Detection and Monitoring of Ionizing Radiation Treatment Using Radiation-Responsive Gel Nanosensors

“…Although the current technology is promising and can have a significant clinical impact, a thorough evaluation of the biocompatibility of these nanosensors is necessary prior to eventual translation for human use. In addition, future formulations can be generated using more biocompatible formulations, including using amino acids as templating agents for nanoparticle formation . Evaluation of the cellular and tissue biocompatibility of these gels, including in live animals, will be part of future work.…”

“…In addition, future formulations can be generated using more biocompatible formulations, including using amino acids as templating agents for nanoparticle formation. 60 Evaluation of the cellular and tissue biocompatibility of these gels, including in live animals, will be part of future work. We will also explore a diverse set of cationic surfactants and their combinations in order to facilitate radiation-induced generated nanoparticles with more uniform shapes and sizes, which may, in turn, improve the efficacy of the gel nanosensor.…”

Biomarker-driven molecular imaging probes in radiotherapy

“…Strengths of applying state-of-the-art imaging probes before, during, and after radiotherapy are briefly listed below: a) Biomarker-specific single/dual/multiple-modality imaging. With the aid of elegant design of probes, such as biomarker-targeted or activated strategies and the use of bifunctional chelators, single/dual/multiple-modality imaging with great sensitivity/tumor penetration, sharp resolution, and enhanced signal-to-noise ratios could be realized 97 - 99 ; b) Radiation-responsive imaging probes, such as a phenylalanine and tryptophan-based amino acid nanosensor gel and a gold-containing gel nanosensor 100 - 102 , have been employed for radiation dosimetry in EBRT and/or RPT to quantitatively assess radiation exposure doses; c) X-ray-activated imaging probes, such as perovskite nanocrystal scintillators 103 , organic phosphorescent scintillators 104 , and probes with the properties of Cerenkov and radioluminescent light enhancement 105 , 106 , as well as organic luminophores with the ability of radio afterglow imaging 107 , have been explored to supplement the contemporary cone beam CT-guided radiotherapy; and d) Probe-mediated immune cell-tracking for monitoring radiotherapy-induced immune response, including the distribution and activity of immune cells. Probe hitchhiking strategies or other direct/indirect cell labelling strategies aid in this tracking procedure 75 , 108 , 109 .…”

Review of nanomaterial advances for ionizing radiation dosimetry

“…A further new colorimetric approach for radiation detection was proposed recently, based upon gold nanoparticles being shaped by amino acids after being exposed to ionizing radiation. 176 A library containing 32 amino acids (20 natural, 7 artificial, and 5 optical isomers) was screened to test their ability to enhance the creation of gold nanoparticles when irradiated to x rays or photons, which was observed as an increase in usual absorbance wavelengths. It was found that aspartic acid, leucine, phenylalanine, threonine, and valine, each tend to template AuNP formation after exposure to ionizing radiation.…”