Polyethylene Glycol-Functionalized Gold Nanorods for Near-Infrared Photothermal Cancer Theranostics

Abstract

Gold nanorods (AuNRs) have strong near-infrared (NIR) photothermal conversion and high X-ray attenuation, which makes them attractive for cancer theranostics. However, their clinical use is limited by the cytotoxic surfactant cetyltrimethylammonium bromide (CTAB) that is used in synthesis. In this study, CTAB was replaced with polyethylene glycol 4000 (PEG-4000) through a single-step ligand exchange procedure. The resulting AuNR-PEG nanoconstructs were characterized and evaluated for photothermal therapy and CT imaging performance. AuNRs were synthesized by seed-mediated growth and subsequently PEGylated. TEM images confirmed rod-shaped morphology with dimensions of 38 ± 2 nm in length and 9 ± 2 nm in width, with an aspect ratio of approximately 4.2. Successful PEGylation was confirmed by multiple characterization methods. UV-Vis spectroscopy showed a red-shift of the longitudinal LSPR peak from approximately 790 nm to 810 nm after PEGylation. XRD confirmed that the gold face-centered cubic crystal structure was preserved. FTIR spectra showed the disappearance of CTAB-specific bands and the appearance of PEG ether bands. XPS confirmed C-O bonding and metallic Au(0). Zeta potential measurements showed a surface charge reversal from +40.8 mV for CTAB-coated AuNRs to −20.2 mV for AuNR-PEG, which confirmed successful ligand exchange. For photothermal performance, AuNR-PEG embedded in agarose tissue phantoms was irradiated with 808 nm NIR light. At a 1:1 nanorod-to-agarose ratio, the temperature reached 60.1°C (ΔT = 37.1°C) within 5 minutes, which is above the 41°C threshold for tumor cell ablation. CT imaging showed that AuNR-PEG produced 79 HU per mg/mL compared to 30.9 HU per mg/mL for iopromide (Ultravist), which is 2.6 times higher attenuation at the same concentration. Cytotoxicity assays were performed in SW480 colorectal cancer cells and CCD 841 normal colon epithelial cells. CTAB-coated nanorods were already toxic to SW480 cells at 31.25 ppm, while AuNR-PEG maintained substantially higher viability. Under 808 nm NIR irradiation, AuNR-PEG caused selective photothermal cell death in SW480 cells, while CCD 841 normal cells were largely spared at the same doses. These results show that PEG-4000 ligand exchange produces biocompatible AuNR-PEG nanoconstructs that retain the NIR photothermal and CT imaging properties required for a dual theranostic platform.