Abstract A051: Optimization of Dual Combination [DOX][NIR] Nanomedicine: Effect of Size Tuning on Photophysical Behavior and Photothermal Efficiency for Enhanced Anti-Tumor Activity
Combination therapies involving chemotherapy and photothermal therapy (PTT) are often limited by mismatched pharmacokinetics and poor tumor localization of individual agents. In this study, we addressed these challenges by synthesizing carrier-free, aqueous nanoparticles (NPs) via the stoichiometric ion-pairing of Doxorubicin (DOX) and the near-infrared dye. Utilizing a controlled reprecipitation method, we successfully tuned the NP hydrodynamic diameter to investigate the relationship between nano-architecture and therapeutic performance. UV-Vis and fluorescence spectroscopy revealed size-dependent molecular packing, significantly influencing the non-radiative decay pathways. Systematic evaluation of the photophysical properties demonstrated that NPs exhibited a peak light-to-heat conversion efficiency, representing improvement over the free dye. This enhancement is attributed to the optimized fluorescence quantum yield of the nano-assembly, which facilitates superior photothermal performance under 808 nm laser irradiation. These results identify a critical size-performance threshold for [DOX][NIR] nanomedicines, providing a scalable and highly efficient platform for synergistic chemo-photothermal (chemo-PTT) cancer eradication. Fatima Abbas, Fatima Abbas. Optimization of Dual Combination [DOX][NIR] Nanomedicine: Effect of Size Tuning on Photophysical Behavior and Photothermal Efficiency for Enhanced Anti-Tumor Activity [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr A052.