Researcher: Jeungyoon Lee
Introduction
Thermal therapies hold great promise for cancer treatment by enabling tumor ablation, tumor microenvironment modulation, and controlled drug delivery. However, their clinical efficacy depends critically on accurate, real-time temperature monitoring. While techniques such as magnetic resonance (MR), ultrasound (US), and photoacoustic (PA) imaging have been employed, their reliance on tissue-specific properties limits their ability to provide calibration-free, reliable temperature measurements across heterogeneous tumor environments. We demonstrated that nanoparticle (NP)-mediated PA thermometry can achieve calibration-free temperature sensing by stabilizing the local aqueous environment around the NPs. Building on this foundation, we aim to extend NP-enhanced PA thermometry to complex tumor models. Thus, this approach could enable accurate, calibration-free temperature mapping across tumor tissues, advancing the precision and effectiveness of thermal therapies.
Methods
AuNSs were synthesized and PEGylated to enhance colloidal stability in physiological environments, such as aqueous and lipid-rich media. TEM imaging confirmed the morphology of PEG-AuNSs (Figure 1A). To assess the temperature dependence of their PA signal, PEG-AuNSs were suspended in water, low-fat (10% olive oil), and high-fat (50% olive oil) solutions. Across 33–43 °C, all samples exhibited similar linear increases in PA signal with temperature (Figure 1B). Linear regression slopes of normalized PA signal versus temperature showed no significant difference among groups (n=3, Figure 1C). These results indicate that PEG-AuNSs retain a water-based local environment, resulting in similar PA thermal response regardless of the surrounding bulk composition.
Discussion
To evaluate this behavior in a more biologically relevant context, AuNSs were internalized by macrophages and embedded in tissue-mimicking phantoms containing 0%, 10%, 30%, or 50% olive oil (Figure 1D). PA signals from AuNS-labeled cells also increased linearly with temperature across all inclusions (Figure 1E), and slopes of PA signal change were not significantly different from the water-only control (n=3, Figure 1F). These results support that appropriate nanoparticle surface chemistry enables NPs to retain aqueous surrounding layers, preserving their PA thermal response even in lipid-rich tissue background.
These findings highlight the potential of NP-mediated, calibration-free PA thermometry for guiding thermal therapies, particularly in heterogeneous tissues where composition is unknown. However, in deep tissues, challenges arise from light scattering and acoustic attenuation that can significantly reduce PA signal strength and signal-to-noise ratio (SNR), limiting temperature sensing accuracy. Therefore, further investigation including in vivo demonstration is required for proving the reliability of the method for guiding the thermal therapies of solid tumor with complex biological tissue properties.
Further reading
[1] J. Lee, K.P. Kubelick, A. Choe, S.Y. Emelianov, “Photoacoustic-guided ultrasound thermal imaging without prior knowledge of tissue composition,” Photoacoustics 33:100554 (2023)