Silica-Gold Nanocomposites Enhance Uptake and Radiosensitization in Prostate Cancer Cell Models

Gold nanoparticles (AuNPs) are promising high atomic number ( high-Z ) radiosensitizers but clinical translation is limited by efficient tumor cell delivery. Here the design and evaluation of gold nanocomposite (NC) architectures to transport high concentrations of AuNPs into prostate cancer cells at an increased internalization rate is reported. Gold NCs (∼50 nm) comprising a silica nanoparticle scaffold were reproducibly synthesized with excellent colloidal stability over several weeks. Efficient NC internalization by prostate cancer PC3 and DU145 cells was confirmed by hyperspectral imaging, fluorescence lifetime microscopy, multiphoton microscopy, and focused ion beam scanning electron microscopy (FIB/SEM). Au/SiAuC NCs comprising 4 nm AuNPs immobilized on silica-coated 20 nm AuNP cores achieved the highest intracellular gold accumulation (PC3: 38 pg/cell; DU145: 40 pg/cell). Critically, the rate of NC gold uptake was significantly faster (14.6 ± 1.98 pg Au/cell/h) than free AuNPs (3.1 ± 1.5 pg Au/cell/h), a property that minimizes the risk of off-target effects. Toxicity studies confirmed that NCs were well tolerated, inducing no significant direct toxicity. Upon irradiation, Au/SiAuC NCs yielded a significant sensitizer enhancement ratio (SER) of 1.34 ( p < 0.05) and a dose-dependent increase in cell death, underpinned by enhanced NC-mediated DNA damage. The combination of high cellular uptake, low intrinsic cytotoxicity, and effective radiosensitization supports the application of this platform in nanomedicine-based radiotherapy.