Recommendations for clinical translation of nanoparticle-enhanced radiotherapy

Abstract

A multi-disciplinary cooperative for nanoparticle-enhanced radiotherapy (NERT) has been formed to review the current status of the field and identify key stages towards translation. Supported by the Colorectal Cancer Healthcare Technologies Cooperative, the cooperative comprises a diverse cohort of key contributors along the translation pathway including academics of physics, cancer and radio-biology, chemistry, nanotechnology and clinical trials, clinicians, manufacturers, industry, standards laboratories, policy makers and patients. Our aim was to leverage our combined expertise to devise solutions towards a roadmap for translation and commercialisation of NERT, in order to focus research in the direction of clinical implementation, and streamline the critical pathway from basic science to the clinic. A recent meeting of the group identified barriers to and strategies for accelerated clinical translation. This commentary reports the cooperative's recommendations. Particular emphasis was given to more standardised and cohesive research methods, models and outputs, and reprioritised research drivers including patient quality of life following treatment. Nanoparticle design criteria were outlined to incorporate scalability of manufacture, understanding and optimisation of biological mechanisms of enhancement and in vivo fate of nanoparticles, as well as existing design criteria for physical and chemical enhancement. In addition, the group aims to establish a long-term and widespread international community to disseminate key findings and create a much-needed cohesive body of evidence necessary for commercial and clinical translation.

Radiobiological Implications of Nanoparticles Following Radiation Treatment

“…A cooperative of stakeholders reported recommendations to standardize reporting on the efficacy of NP‐enhanced radiotherapy, highlighting metrics such as NP cellular uptake and cell survival (using fitting parameters α and β obtained from the linear‐quadratic (LQ) model), as well as quoting an enhancement ratio at a dose level of 2 Gy. [ 27 , 28 ] These reports also highlighted that although the α/β ratio would indicate changes in radiosensitivity due to the addition of NPs, no study has currently incorporated this metric within their analysis of the enhancement effect. An interesting aspect of this is to compare findings with the literature on samples irradiated with higher linear energy transfer (LET) radiation, such as protons, which show an increased relative biological effectiveness (RBE) due to more densely ionizing incident radiation.…”

Intercomparison of Radiosensitization Induced by Gold and Iron Oxide Nanoparticles in Human Glioblastoma Cells Irradiated by 6 MV Photons

“…All survival fractions were normalized for control plating efficiency (0 Gy). The sensitization enhancement ratio at a 10 % survival (SER 10% ) 5,45,46 was derived to quantify the effectiveness of the NPs action: SER 10% = Dose at 10% survival without NPs (D control ) Dose at 10% survival with NPs (D NPs )…”

“…The overall NP effect on cell death, expressed in terms of the sensitization enhancement ratio at a 10 % survival (SER 10% ) and the α and β values were extracted from the cell survival curves. Fold change in the α/β ratios between treated and untreated groups were also obtained and used as an indicator of the relative importance of lethal and potentially lethal damage to the cells 9,45,46 . All such parameters extracted from the survival curves are displayed in Table 2.…”

Gold Nanoparticle DNA Damage by Photon Beam in a Magnetic Field: A Monte Carlo Study

“…Therefore, gold nanoparticle-enhanced radiotherapy has become popular, resulting in many studies on the basic science and clinical application [ 12 , 13 , 14 , 15 ]. Many preclinical works have been carried out, and clinical trials are being conducted, building a potential roadmap to clinical implementation [ 16 ].…”