<p>Monte Carlo Evaluation of Dose Enhancement Due to CuATSM or GNP Uptake in Hypoxic Environments with External Beam Radiation</p>

Abstract

Purpose: Most solid tumors contain areas of chronic hypoxia. Gold nanoparticles (GNP) have been extensively explored as enhancers of external beam radiation; however, GNP have lower cellular uptake in hypoxic conditions than under normoxic conditions. Conversely, the chelator diacetyl-bis (N(4)-methylthiosemicarbazonato) copper II (CuATSM) deposits copper in hypoxic regions, allowing for dose enhancement in previously inaccessible regions. Methods: External beam sources with different spectra were modeled using a Monte Carlo code (EGSnrc) to evaluate radioenhancement in a layered model with metal solutions. Also considered was a simple concentric layered tumor model containing a hypoxic core with each layer varying in concentrations of either copper or gold according to hypoxic conditions. Low energy external photon beams were then projected onto the tumor to determine the regional dose enhancement dependent on hypoxic conditions. Results: Dose enhancement was more pronounced for beam spectra with low energy photons (225 kVp) and was highly dependent on metal concentrations from 0.1 g/kg to 100 g/kg. Increasing the depth of the metallic solution layer from 1 cm to 6 cm decreased dose enhancement. A small increase in the dose enhancement factor (DEF) of 1.01 was predicted in the hypoxic regions of the tumor model with commonly used diagnostic concentrations of CuATSM. At threshold concentrations of toxic subcutaneous injection levels, the DEF increases to 1.02, and in simulation of a high concentration of CuATSM, the DEF increased to 1.07. High concentration treatments are also considered, as well as synergistic combinations of GNP/CuATSM treatments. Conclusion:The research presented is novel utilization of CuATSM to target hypoxic regions and act as a radiosensitizer by the nature of its ability to deposit copper metal in reduced tissue. We demonstrate CuATSM at high concentrations with low energy photons can increase dose deposition in hypoxic tumor regions.

Nanoparticle‐based applications for cervical cancer treatment in drug delivery, gene editing, and therapeutic cancer vaccines

“…This nanocarrier system not only delivered siRNA that targeted HPV E6 gene efficiently, but inhibited xenograft tumors, which derived from HeLa cells specifically. In addition, increasing evidences showed that metallic NPs could improve radiosensitivity and attenuate systemic toxicity at the same time (Martinez et al, 2020 ; Pagáčová et al, 2019 ). Yang et al ( 2020 ) developed one biocompatible material PEGylated platinum nanoflowers (Pt NFs).…”