Abstract P4-12-27: Exploring Stimulation Response of Cisplatin Prodrugs and Integrating Photothermal-Photoacoustic Dual-Modal Theranostics in Triple-Negative Breast Cancer through Ozone-mediated Photothermal Catalytic Nanosystem

Abstract Background: The combination of chemotherapy with immune checkpoint inhibitors shows a synergistic anti-tumor effect. Nevertheless, the issues of chemoresistance and the significant toxicity associated with combined treatments pose substantial challenges. We have successfully synthesized a fluorocarbon chain-modified cisplatin precursor (PtF) in previous research, showing optimized controlled-release properties, robust anti-tumor activity, high efficiency, and well tolerated toxicity. Methodology: In this study, we utilize the PtF prodrug as a delivery vehicle, encapsulating gold nanoparticles to construct the PLAOP system. The near-infrared (NIR)-I light irradiation was applied as activator of the photothermal and photoacoustic effect. Results: This study evaluated the photothermal effect of PLAOP upon NIR-I light irradiation, which enables photoacoustic imaging of tumors by inducing thermoelastic expansion of the gold nanoparticles. We also elucidated the role of the photothermal effect produced by NIR I-activated PLAOP in catalyzing the generation of reactive oxygen species (ROS) from ozone. Moreover, the synergistic application of NIR I with PLAOP leverages ROS-GSH modulation to govern the responsive release of platinum-based prodrugs, thereby achieving dual-mode photothermal and photoacoustic visualization in triple-negative breast cancer (TNBC). This strategy enables precise tumor imaging and ensures a controlled, high-efficacy release of both cisplatin and ROS, which not only potentiates the anti-tumor therapy but also triggers immune cell death. This study presents a new strategy for theranostics for the combined treatment with ICBs in TNBC, where traditional therapeutic targets are lacking. Citation Format: Dan Zheng, Ting Luo, Hubing Shi, Tianyue Xu, Linlin Song. Exploring Stimulation Response of Cisplatin Prodrugs and Integrating Photothermal-Photoacoustic Dual-Modal Theranostics in Triple-Negative Breast Cancer through Ozone-mediated Photothermal Catalytic Nanosystem [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-12-27.