Nanoparticle radio-enhancement: principles, progress and application to cancer treatment

Abstract

Enhancement of radiation effects by high-atomic number nanoparticles (NPs) has been increasingly studied for its potential to improve radiotherapeutic efficacy. The underlying principle of NP radio-enhancement is the potential to release copious electrons into a nanoscale volume, thereby amplifying radiation-induced biological damage. While the vast majority of studies to date have focused on gold nanoparticles with photon radiation, an increasing number of experimental, theoretical and simulation studies have explored opportunities offered by other NPs (e.g. gadolinium, platinum, iron oxide, hafnium) and other therapeutic radiation sources such as ion beams. It is thus of interest to the research community to consolidate findings from the different studies and summarise progress to date, as well as to identify strategies that offer promising opportunities for clinical translation. This is the purpose of this Topical Review.

Highly Porous Hybrid Metal–Organic Nanoparticles Loaded with Gemcitabine Monophosphate: a Multimodal Approach to Improve Chemo‐ and Radiotherapy

“…The radioenhancement effect is due to the succession of physicochemical processes as described elsewhere for high‐Z compounds and dense NPs . Of note we present here a radioenhancement effect with porous low density NPs containing iron .…”

“…[15] Of note we present here a radioenhancement effect with porous low density NPs containing iron. [15] Briefly, the radioenhancement observed with the nanoMOFs may be explained by the activation of Fe atoms interacting with γ rays, followed by de-excitation and emission of electrons. The interaction of emitted electrons with surrounding water molecules is responsible for the production of hydroxyl radicals, which are toxic for the cells.…”

“…In this case, cell killing drastically increased as witnessed by the REF of 1.83 (as compared to 1.19 for nanoMOF, and 1.35 for Gem‐MP alone) and by the DEF (4 Gy) up to 6.47 (as compared to 1.53 for nanoMOF and 2.23 for Gem‐MP). To the best of our knowledge, the REF obtained with high‐Z NPs is in the range of 1.1 to 1.6 . Thus, the amplification effect obtained by Gem‐MP loaded nanoMOF is among the highest ever reported.…”

“…Briefly, the radioenhancement observed with the nanoMOFs may be explained by the activation of Fe atoms interacting with γ rays, followed by de‐excitation and emission of electrons. The interaction of emitted electrons with surrounding water molecules is responsible for the production of hydroxyl radicals, which are toxic for the cells . Thus, the toxicity of a radiation treatment increases with the number of electrons interacting with water molecules.…”

“…In addition to the benefits of NPs for drug delivery, the potential value of metal based NPs as radioenhancers has been discovered in 2000 . Currently, there are several types of high‐Z NPs in clinical development, including Au NPs, Gd NPs, and crystalline HfO 2 NPs endowed with a targeting coating . More recently, porous Hf based nanoscale metal‐organic frameworks (nanoMOF) outperformed dense HfO 2 NPs .…”