The future of nanosized radiation enhancers

Abstract

Radiotherapy has a universal and predictable mode of action, that is, a physical mode of action consisting of the deposit of a dose of energy in tissues. Tumour cell damage is proportional to the energy dose. However, the main limitation of radiotherapy is the lack of spatial control of the deposition of energy, that is, it penetrates the healthy tissues, damages them and renders unfeasible delivery of an efficient energy dose when tumours are close to important anatomical structures. True nanosized radiation enhancers may represent a disruptive approach to broaden the therapeutic window of radiation therapy. They offer the possibility of entering tumour cells and depositing high amounts of energy in the tumour only when exposed to ionizing radiations (on/off activity). They may unlock the potential of radiation therapy by rendering the introduction of a greater energy dose, exactly within the tumour structure without passing through surrounding tissues feasible. Several nanosized radiation enhancers have been studied in in vitro and in vivo models with positive results. One agent has received the authorization to conduct clinical trials for human use. Opportunities to improve outcomes for patients receiving radiotherapy, to create new standards of care and to offer solutions to new patient populations are looked over here.

Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date

“…Incorporation of a high electron density material maximizes x-ray interactions producing a larger number of excited electrons and in turn forming more reactive radical species (77). Developed for injection into a tumor site these particles are designed to undergo cell uptake.…”

Combining ultrasmall gadolinium-based nanoparticles with photon irradiation overcomes radioresistance of head and neck squamous cell carcinoma

“…2 High-Z elements have large photon-interaction cross sections and produce a large variety of secondary emissions, all of which leading to the generation of reactive oxygen species (ROS). Since the pioneering works of Mc Carthy and Weissleder 3 on multifunctional nanoparticles, different architectures have been developed such as doped hybrid silicas, quantum dots, carbon nanotubes, iron oxides, gold nanoparticles, FePt nanoclusters, and lanthanide oxide nanoparticles.…”

Nanopharmaceuticals (part 2): products in the pipeline

“…53 In particular, surface-modified negatively charged NPs made of hafnium oxide ("NBTXR3," see Table 2) are currently being explored as selective radio enhancers for the local treatment of solid tumors. 53,54 Upon activation with ionizing radiation, these electron-dense particles generate large quantities of reactive oxygen species inside the tumor, which in turn are ultimately responsible for the cellular damage. The general approach of using NP-based radio enhancers is illustrated in Figure 5.…”

“…Finally, sodium trimetaphosphate is added and the pH adjusted to 6.7-7.5. 54,55 Transmission electron microscopy of NBTXR3 NPs shows the presence of NPs with a spherical shape as well as the formation of clusters or aggregates. 55 The particle size of hafnium oxide NPs, measured by DLS, revealed a hydrodynamic diameter of 50 nm and a polydispersity index around 0.100, with a negatively charged surface (-50 mV), as estimated by zeta potential measurements.…”