Abstract 670: Specific ROS generation and monitoring in cancer using radioactive gold nanoparticle

Abstract

Radiotherapy is a key treatment and is beneficial in the treatment of about 50% of all cancer patients. Such treatment relies on the deposition of energy (the dose) in tumour cells, typically by irradiation with either high-energy gamma rays or X-rays (photons), or energetic beams of ions, sufficient to damage the cancer cells or their vasculature and thus induce tumour death or nutrient starvation. However, like chemotherapy, photon radiotherapy is non-specific, since a significant dose can be delivered to healthy tissue along the track of the photons, in front and behind the tumour. Therefore, recently several research groups have proposed the use of specifically targeted noble-metal nanoparticles irradiated by radiation as an effective therapeutic tool for treating various malignancies with minimum collateral damage to healthy tissue. In general, the photoelectric absorption cross sections of radiosensitive materials directly depend on atom radius, and thus their radiotherapy effects also depend on atom radius. This physical principle determines that gold (atomic-number Z=79) has a stronger radiation enhancement effect by photoelectric effect. Loading with gold nanoparticles (AuNPs) is one of the promising candidates in this area. Gold NPs have a larger atomic radius than gold atom (~0.17 nm), and thus should have a stronger radiation enhancement effect than gold atom. During irradiation, this results in an enhancement of the energy deposition in the vicinity of the gold particles generate the ROS on the surface due to the generation of photoelectrons, Auger electrons, and characteristic X-rays. ROS play important roles in various cellular process. In particularly, at sufficiently high concentrations, ROS could become an effect that is utilized for various therapeutic application such as apoptosis. Herein, we synthesized the radiosensitizer PEGylated gold nanoparticles (RPAuNPs) for generation and measuring of ROS on surface by radiation exposure. First, gold nanoparticles (AuNPs) was prepared by one-pot synthesis and the sharpness and size were efficiently controlled by adjusting the amount of reducing agent. Furthermore, they were replaced with heterobifunctional PEG (COOH-PEG-SH) not only to serve as a biocompatible stabilizer (PAuNPs) and but also to conjugate Dihydrorhodamine 123 (DHR 123) (RPAuNPs) as ROS sensor. Well-engineered formation of RPAuNPs was verified by transmission electron microscopy (TEM) showing their overall size of 50 nm. In addition, UV-Vis data strongly demonstrated successful synthesis. We evaluated their functional use in inducing ROS and the results showed that our radiosensitizing agents exhibited the feasibility of effective ROS generation under x-ray radiation. And we investigated there in vitro/in vivo imaging and therapeutic efficacies, optical properties, biocompatibility for tumor cell.

Citation Format: Jihye Choi, Yoon Woo Koh, Hyung Kwon Byeon, Guillem Pratx, Jaemoon Yang. Specific ROS generation and monitoring in cancer using radioactive gold nanoparticle [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 670.