Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation

Abstract

Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo–generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.

Potential of using cerium oxide nanoparticles for protecting healthy tissue during accelerated partial breast irradiation (APBI)

“…3 [21,22]. The empirical relation between the electron energy loss with distance traveled dE / dR (keV/μm) and the residual range R (μm) ( R = R tot − r e ) is based on Cole’s formula, where R tot is the total range of the electron for a kinetic energy E and r e is the distance from the electron emission site [23]: $$\frac{dE}{dR}=3.316{(R+0.007)}^{-0.435}-0.0055R^{0.33}.$$…”

Enhancing radiotherapy for lung cancer using immunoadjuvants deliveredin situfrom new design radiotherapy biomaterials: a preclinical study

“…It is also possible to load the IA along with gold nanoparticles (GNP). Because gold nanoparticles are biocompatible, can serve as radiosensitizing agent (Ngwa et al , 2014; Hainfeld et al , 2008; Hao et al , 2015) and can be easily functionalized with IA (Cao-Milan and Liz-Marzan, 2014), the GNP could be used as carriers for IA in our model. Our previous studies have highlighted the feasibility of loading radiotherapy biomaterials with GNP (Ngwa et al , 2014).…”

Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications

“…Delivery of NBRs via inhalation is a technique in which tumors, such as lungs cancers, can be radiosensitized with NBRs. Lung cancers are among the leading cause of cancer-associated mortality and generally have short survival rates of about 16% within five years [68,69]. However, radiation boosting can substantially increase the survival rate for patients with lung cancers, but is restricted by healthy tissue toxicity due to the respiratory motion [68,[70][71][72].…”

“…Lung cancers are among the leading cause of cancer-associated mortality and generally have short survival rates of about 16% within five years [68,69]. However, radiation boosting can substantially increase the survival rate for patients with lung cancers, but is restricted by healthy tissue toxicity due to the respiratory motion [68,[70][71][72]. The proposed treatment strategy to overcoming the limitations is to increase the dose to the tumor volume, while carefully sparing the surrounding normal lung tissue by increasing local radiosensitization via inhalation nanoparticles, as seen in Figure 1B, and decreasing the dose to balance complications and cancer cure [1,68].…”

“…Combined chemoradiotherapy is the best strategy for boosting the radiation dose to the tumor. However, studies have shown that only about 5% of NPs administered via intravenous (IV) routes reach the lungs [1,68,73]. Conversely, delivery of NPs via inhalation leads to the accumulation of NPs in the lungs, limiting the escape of the NPs into the systemic circulation, thereby limiting systemic toxicity [73].…”