RGD-functionalized gold nanoparticles radiosensitize prostate cancer cells and xenografts for HDR-BT

Prostate cancer is often treated with radiation therapy, including high-dose-rate brachytherapy (HDR-BT), but improving its efficacy remains a challenge. Gold nanoparticles (GNPs) show promise as radiosensitizers, yet their application with HDR-BT, especially considering surface functionalization effects on targeting and uptake, is underexplored. Understanding how active cellular targeting via the integrin-binding domain RGD impacts radiosensitization in vivo is crucial for advancing clinical translation and optimizing treatment strategies.

Researchers systematically compared the radiosensitization efficacy of non-targeted PEGylated GNPs versus actively targeted PEG-RGD GNPs in PC3 prostate cancer cells (2-D and 3-D cultures) and male NRG mice xenografts. In vitro, cells were dosed at 10 μg [Au]/mL. Mice received intratumoral injections of 50 μL at 2 mg [Au]/kg bodyweight. All samples were irradiated via a 192-Ir source delivered from a clinical HDR-BT afterloader, with primary endpoints including cell survival fraction, DNA DSBs (double-strand breaks), and tumor volume growth.

Non-targeted PEGylated GNPs did not elicit any radiosensitization in 2-D, 3-D, or in vivo models. In contrast, RGD-functionalized GNPs demonstrated significant efficacy. In 2-D cell cultures, they elicited a 17% (p=0.001) reduction in survival fraction and 33% (p=0.005) greater DNA DSBs compared to controls. In 3-D spheroid cultures, RGD-GNPs achieved a 57% (p<0.0001) reduction in spheroid growth 14 days post-irradiation. The most impactful finding in vivo was:

In a preclinical mouse xenograft model, RGD-GNPs significantly reduced tumor volume growth by 28% (p=0.005) 20 days post-irradiation compared to the irradiated control group. Importantly, no observable signs of acute toxicity were reported from either the radiation delivery or the administered GNPs, highlighting the potential for a favorable safety profile. This underscores active cellular targeting via integrin-binding RGD as a critical determinant of radiosensitization efficacy.