Enhanced proton treatment in mouse tumors through proton irradiated nanoradiator effects on metallic nanoparticles

Abstract

The impact of protons on metallic nanoparticles (MNPs) produces the potent release of MNP-induced secondary electrons and characteristic x-rays. To determine the ability of secondary radiations to enhance proton treatment, the therapeutic irradiation of tumors was investigated in mice receiving 100-300 mg MNPs/kg intravenously prior to single dose, 10-41 Gy, proton irradiation. A proton beam was utilized to irradiate nanoparticles with a single Bragg peak set to occur inside a tumor volume (fully absorbed) or to occur after the beam had traversed the entire body. The dose-dependent increase in complete tumor regression (CTR) was 37-62% in the fully-absorbed irradiation group or 50-100% in the traversing irradiation group, respectively, compared with the proton-alone control mice (p < 0.01). One year survival was 58-100% versus 11-13% proton alone. The dose-dependent increase of intracellular reactive oxygen species level was 12-36% at 10 Gy compared with the proton-alone control cell. Therapeutic effective drug concentration that led to 100% CTR with a proton dose of 31 Gy was measured either 41 µg Au/g tissue or 59 µg Fe/g tissue. MNP-based proton treatment increased not only percent CTR and survival in vivo but also ROS generation in vitro, suggesting tumor dose enhancement from secondary radiation as one potent pathway of therapeutic enhancement.

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

“…beam, and found significant reduction in the tumour volume compared to the control. This work was followed by another paper which found the reactive oxygen species in irradiated tumour cells containing nanoparticles was 12-36 % higher than in the control (Kim et al, 2012).…”

“…There have been a limited number of reports where relatively high energy particles (50 MeV or above) have been used to irradiate cells or tumours (Kim et al, 2012, Kim et al, 2010 …”

Enhancement of Tumor Regression by Coulomb Nanoradiator Effect in Proton Treatment of Iron-Oxide Nanoparticle-Loaded Orthotopic Rat Glioma Model: Implication of Novel Particle Induced Radiation Therapy

“…Recently, our laboratory found proton-impact high-Z nanoparticles produced CNR-based dose enhancement effect that led to a large therapeutic enhancement on nanoparticle-loaded mouse tumor model in either SOBP [3] or traversing Bragg peak irradiation [4]. Other groups also demonstrated the enhancement of cytotoxicity in their ion beam-impact in vitro studies on either platinum or gold-loaded cells [5,6].…”

“…Other groups also demonstrated the enhancement of cytotoxicity in their ion beam-impact in vitro studies on either platinum or gold-loaded cells [5,6]. Therapeutic enhancement was believed to have relevance to dose-enhancement effect from burst emission of low-energy electrons by Auger cascades of directly-impact ionized atom and interatomic relaxation process (IRP)-driven ionization from surrounding neutral atoms, collectively termed as Coulomb nanoradiator (CNR) [4,7].…”

Geant4 interaction model comparison for dose deposition from gold nanoparticles under proton irradiation

“…Therefore, new methods are under investigation in order to boost the dose at the tumour site, while sparing the adjacent tissues. Gold nanoparticles (GNPs) have demonstrated radiosensitization potential in vivo and in vitro, under irradiation with x-rays, electrons, and protons (Hainfeld et al 2004, Liu et al 2010, Polf et al 2011, Kim et al 2012. While the radiosensitization effect may also be attributed to biological or chemical mechanisms, the physical interaction of the radiation with the GNPs is the main contributing factor to the effect through the production of secondary radiation.…”