Theranostic Gold Nanoparticles for Enhanced Prostate Cancer Radiotherapy

Abstract

Theranostic gold nanoparticles (GNPs) were engineered to enhance external-beam radiotherapy for prostate cancer while enabling quantitative imaging readouts. I synthesized biocompatible, polyphenol-functionalized GNPs using epigallocatechin gallate (EGCG-GNPs) and curcumin (Curc-GNPs), optimized for colloidal stability, cell-receptor affinity, and antioxidative properties. Comprehensive physicochemical characterization (DLS/ζ-potential, TEM, UV–Vis) and analytical assays (HPLC for drug loading; ICP-MS for Au quantification) established reproducible formulations. In vitro studies in PC-3 cells demonstrated efficient cellular uptake and radiosensitization, evidenced by reduced clonogenic survival compared with radiation alone. In vivo, murine and canine models were used to evaluate biodistribution, acute/sub-acute toxicity, and imaging. Computed-tomography (CT) phantom and tissue studies confirmed a linear relationship between Hounsfield units and gold concentration, enabling noninvasive estimation of intraprostatic nanoparticle burden. A physiologically based pharmacokinetic (PBPK) model captured organ kinetics and supported translation of exposure–response. Finally, I piloted an image-guided intra-arterial delivery paradigm adapted from prostatic arterial embolization: nanoparticle infusion into prostate lobes followed by embolization to promote local retention, reduce systemic exposure, and potentiate radiation dose deposition. This minimally invasive procedure was tested in 3 lab beagles and 1 clinical canine case with naturally occurring prostate cancer. Collectively, these data establish a dual-functional GNP platform that couples CT-visible quantification with meaningful radiosensitization, laying the preclinical and procedural groundwork for image-guided nanoparticle-augmented radiotherapy in prostate cancer.