The potential of gold nanoparticles (GNPs) in therapeutic and diagnostic cancer applications is becoming increasingly recognized. These biologically compatible particles can be easily synthesized, tuned to different sizes, and functionalized by conjugation to various biologically useful materials. Efficient and specific delivery to tumor tissue can then be accomplished either by passive accumulation in leaky tumor vessels and tissue, or by directly targeting tumor-specific biomarkers. Tumor-localized GNPs can serve as both adjuvants for enhancing the efficacy of radiation therapy and also as contrast agents for various imaging modalities. In this review, we will discuss recent advancements and future potential in the application of GNP as both a radiosensitizer and an imaging contrast agent. Due to their versatility and biocompatibility, gold nanoparticles may represent a novel theranostic adjuvant for radiation applications in cancer management.

Glioblastoma (GBM) is the most common primary malignant astrocytoma characterized by extensive invasion, angiogenesis, hypoxia, and micrometastasis. Despite the relatively leaky nature of GBM blood vessels, effective delivery of antitumor therapeutics has been a major challenge due to the complications caused by the blood-brain barrier (BBB) and the highly torturous nature of newly formed tumor vasculature (blood tumor barrier-BTB). External beam radiotherapy was previously shown to be an effective means of permeabilizing central nervous system (CNS) barriers. By using targeted short-ranged radionuclides, we show for the first time that our targeted actinium-225-labeled α_vβ₃-specific liposomes (²²⁵Ac-IA-TLs) caused catastrophic double stranded DNA breaks and significantly enhanced the permeability of BBB and BTB in mice bearing orthotopic GBMs. Histologic studies revealed characteristic α-particle induced double strand breaks within tumors but was not significantly present in normal brain regions away from the tumor where BBB permeability was observed. These findings indicate that the enhanced vascular permeability in these distal regions did not result from direct α-particle-induced DNA damage. On the basis of these results, in addition to their direct antitumor effects, ²²⁵Ac-IA-TLs can potentially be used to enhance the permeability of BBB and BTB for effective delivery of systemically administered antitumor therapeutics. Mol Cancer Ther; 16(10); 2191-200. ©2017 AACR.