The role of mitochondrial function in gold nanoparticle mediated radiosensitisation

Abstract

Gold nanoparticles (GNPs), have been demonstrated as effective preclinical radiosensitising agents in a range of cell models and radiation sources. These studies have also highlighted difficulty in predicted cellular radiobiological responses mediated by GNPs, based on physical assumptions alone, and therefore suggest a significant underlying biological component of response. This study aimed to determine the role of mitochondrial function in GNP radiosensitisation. Using assays of DNA damage and mitochondrial function through levels of oxidation and loss of membrane potential, we demonstrate a potential role of mitochondria as a central biological mechanism of GNP mediated radiosensitisation.

Actual questions raised by nanoparticle radiosensitization

“…The second pattern shows no initial increase in foci numbers but a significant difference with the control becomes apparent with increasing time. It is the case for 1.9 nm Aurovist ® NP (Jain et al, 2011;Taggart et al, 2014) and 2.7 nm tiopronin-coated NP (Cui et al, 2014). The same phenomenon was observed for titanate nanotubes (Mirjolet et al, 2013), hydroxyapatite NP (Chu et al, 2013), PEGylated nanogel containing 8 nm gold NP (Yasui et al, 2014).…”

“…Later, other facts have added grist to this mill. Among them, the lower cell survival observed when cells are exposed to gold NP before bleomycin (a radiomimetic molecule causing DNA DSB) compared to bleomycin alone (Jain et al, 2011), the dose dependency of the enhancements factor (whatever their mathematical expressions) as mentioned in Taggart et al (Taggart et al, 2014) or their energy dependency in the keV range (Rahman et al, 2014) with maxima at energies different from the edges. At first sight, some results such as the enhancement observed at MeV energy (Geng et al, 2011) or for low-Z elements were pinned up to this "biological" table.…”

Targeted nanoparticles for tumour radiotherapy enhancement—the long dawn of a golden era?

“…However, the mechanism of action leading to increased radiation-induced cell death mediated by NP is not yet fully understood. An increased generation of reactive oxygen species by secondary water radiolysis (29) as well as a potential role of mitochondria as biological mechanisms contributing to NP-mediated enhancement of radiation treatment (30) have been discussed. A direct functional proof for enhanced dose delivery could be the analysis of initial DNA damage foci, such as gamma-H2AX or 53BP1, in tumour and neighbouring normal tissue of an experimental model system.…”

Silver nanoparticles outperform gold nanoparticles in radiosensitizing U251 cells in vitro and in an intracranial mouse model of glioma

“…5 Studies have implicated that the biological mechanisms of AuNPs radiosensitization may be involved in cell cycle arrest and oxidative stress-mediated apoptosis, necrosis, or DNA damage. [6][7][8] The effectiveness of AuNPs as a potential radiation sensitizer has been determined in multiple cancer cell lines and radiation sources and through Monte Carlo calculations. 5 However, whether AuNPs can also sensitize glioma cells to radiation at clinically relevant megavoltage energies is still unclear.…”