Trimerization-Enhanced NIR-II/Photoacoustic Nanoprobes for Precision Osteosarcoma Imaging
S. L. Lu, Jing Wu, Shuxin Lyu, Yu Yifeng, Jong Seung Kim, Ruiping Zhang, Yuling Xiao, Xuechuan Hong, Xiaodong Zeng
Abstract
High Resolution Image Download MS PowerPoint Slide The integration of photoacoustic imaging (PAI) and near-infrared II (NIR-II) fluorescence imaging holds transformative potential for cancer diagnostics but faces challenges in developing high-performance dual-modal contrast agents. We report tH7@CT8, an organic nanoprobe engineered through fluorophore trimerization to address the photothermal conversion efficiency limitations of small-molecule agents. Trimerization of the [1,2,5]thiadiazolo[3,4-g]quinoxaline fluorophore derivative H7 induced aggregation, suppressing fluorescence quantum yield (0.11% vs 0.42% monomer) while amplifying PTCE to 43.1%. Encapsulation within an osteosarcoma-targeting amphiphilic matrix yielded nanoparticles (72 ± 19 nm) with 4-fold enhanced tumor uptake versus nontargeted controls. In orthotopic osteosarcoma models, tH7@CT8 enabled PAI detection and real-time NIR-II guidance with signal (tumor)-to-background ratios >12:1. This work establishes a molecular design strategy to reconcile depth-resolution trade-offs in oncology while advancing organic contrast agents toward clinical translation.