Generating a Systemic Anticancer Immune Response Via Nanoparticle-Mediated Photothermal Immunotherapy
Abstract
Purpose
Augment immunogenic photothermal therapy (PTT) with a novel near-infrared (NIR) plasmonic nanoparticle platform to investigate photothermal immunotherapy treatment schemes. By leveraging the photothermal stability and biocompatibility of armored-core gold nanostar nanoparticles (AC-GNS), tumor ablation is achieved while avoiding off-target heating. Immunogenic cell death induced by nanoparticle-mediated PTT, in combination with clinically relevant immune checkpoint inhibitors, generated a long-lived, systemic anticancer immune response.
Methods
AC-GNS were developed to provide efficient photothermal transduction under near-infrared laser irradiation. Nanoparticle structure and optical properties were characterized using transmission electron microscopy, optical absorption spectroscopy, surface-enhanced Raman spectroscopy, and photoacoustic measurements. In vivo studies were performed in murine tumor models treated with AC-GNS-mediated PTT. Photoacoustic computed tomography (PACT) was used to monitor nanoparticle distribution and obtain real-time, volumetric temperature maps. Thermal dose metrics were derived from spatiotemporal temperature data. Treatment response was evaluated by tumor control, survival, and flow cytometry, with combination studies incorporating immune checkpoint blockade to assess systemic effects.
Results
AC-GNS exhibited enhanced photothermal and photoacoustic stability relative to conventional gold nanostars, with a NIR photothermal conversion efficiency of 86.9%, enabling reproducible thermal dose delivery. PACT provided noninvasive, volumetric monitoring of intratumoral temperature evolution, supporting thermal control. AC-GNS-mediated PTT achieved local tumor control, with 100% survival in a single-tumor model and no treatment-related toxicity after 6 months. In dual-tumor models, PTT combined with immune checkpoint inhibition significantly improved survival outcomes compared to single-modality treatments alone and produced regression of untreated secondary tumors, consistent with systemic anti-tumor immune activation.
Conclusion
This work introduces the AC-GNS nanoparticle platform as a stable photothermal transducer to mediate immunogenic PTT and demonstrates the utility of photoacoustic thermometry for thermal dose monitoring. Results provide a quantitative framework for investigating photothermal immunotherapy treatment schemes and support the development of adaptive strategies to enhance systemic anti-tumor immunity.