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

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 radiation-responsive 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.