Nanoparticles for Radiation Therapy Enhancement: the Key Parameters

Abstract

This review focuses on the radiosensitization strategies that use high-Z nanoparticles. It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy. Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist. In particular, we described and evaluated the influence of X-rays energy spectra using a numerical analysis. We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy. Pointing out the critical parameters of high-Z nanoparticles radiosensitization, this review is expected to contribute to a larger preclinical and clinical development.

Keywords: Cancer; Nanoparticles; Photodynamic therapy.; Radiation therapy; Radiobiology; Radiosensitization.

Figure 1

Depth-dose curves normalized at the depth of maximum for 100 kV, 250 kV and 6 MeV beams (kV = photons, MeV = electrons).

Figure 2

Survival curve example. Illustration of our DMF assessment strategy.

Figure 3

Plot of the calculated DMF values from publications versus beam energy. For energies up to 200 kV, we identified 21 publications dealing with in vitro, 2 in vivo and 2 with both in vitro and in vivo experiments during the period 2008-2014. In the range from 200 kV to 1 MV, 3 in vitro publications were studied. Upon in vitro experiments, the DMF varies from 0.1 to 1.2. Lower values (which are representative of a high radiosensitization) were observed for lower energies. Concerning high-energy beams, 13 publications were analyzed for in vitro, 1 for in vivo experiments and 1 for both; 1 used a 4 MV beam, 13 a 6 MV, 1 a 10 MV and 1 a 15 MV. Upon in vitro experiments, the DMF varies from 0.7 to 0.8 for passive GNP, 0.5 for PEG-coated GNP and 0.6 for a Photofrin® and quantum dots combination.

Figure 4

Example of a standard irradiation setup for a 6 MV irradiation of a cell-well plate placed at the linear accelerator's isocenter under 5 cm of water-equivalent slabs.

Figure 5

Interactions of X-rays with NPs result directly or indirectly in the production of secondary species: photons, electrons and later ROS. Secondary photons or electrons are mostly generated either by photoelectric or Compton effect. The photoelectric effect interaction probability varies with Z⁴ or Z⁵ and dominant until the incident photon energy reaches ≈ 500 keV.

Figure 6

(A) Illustration of a clinical scenario where a volume (blue) has to be irradiated while a part of an organ (green) has to be protected. (B) A simple anterior beam is irradiating the blue volume. (C) The beam energy is maximum in the irradiation field and is reduced out of the field. (D) Given that the interaction probability is higher for low-energy photons, the radiosensitization in presence of NPs should be higher out of the irradiation field. In this case, the green volume that has to be protected would be in the most radiosenzitized area.

Figure 7

Luminescence of APF probe after X-rays excitation of nanoparticles composed of a Tb₂O₃ core, polysiloxane shell in which and porphyrins are covalently linked.