Short Wavelength Infrared Diimmonium Nano-Agents for Photoacoustic Imaging

Abstract Photoacoustic imaging (PAI) as an innovative biomedical imaging modality shows high contrast and superior spatial resolution, yet remains limited by underdeveloped second near-infrared (NIR-II, 1000-1700 nm) contrast agents, particularly neglecting the NIR-IIb (1500-1700 nm) window. In this work, we designed a new class of diimmonium (DB)-based dicationic nano-agents (DB·2X, X = TFSI - , B(C 2 O 4 ) 2 - , or BF 4 - ) for 1700 nm excitation PAI. Density functional theory (DFT) calculations reveal that dicationic DB 2+ exhibits a dramatically reduced excitation energy (1.24 eV) and enhanced oscillator strength (f = 1.11) by molecular engineering, attributed to a symmetry-allowed local excitation mechanism for electronic restructuring. Single-crystal X-ray diffraction further demonstrates the intermolecular spacings >5.0 Å in DB·2X aggregates, facilitating optimized non-radiative transitions for amplified PAI signals. In vivo study using different disease models shows that DB·2TFSI nano-agents under 1700 nm excitation can achieve higher signal-to-background ratio and minimized interference from endogenous chromophores compared to conventional 1064 nm excitation. Biocompatibility assessments confirm low cytotoxicity, underscoring potential for further development of DB·2TFSI nano-agents. This work delivers a robust molecular design paradigm for non-radiative decay optimization, and for the first time establishes 1700 nm-excitable PAI nano-agents, paving the way for tissue high-quality biomedical imaging.