Nanoparticles of non-porphyrinic covalent organic frameworks as contrast agents for photoacoustic imaging

Abstract

Photoacoustic imaging (PAI) is an emerging biomedical modality offering non-invasive, high-resolution imaging with molecular contrast. Its effectiveness for molecular imaging is improved by using external contrast agents such as dyes and nanostructures, which enable targeted imaging, deeper tissue penetration, and enhanced diagnostic accuracy. However, the clinical translation of these agents has been hindered by limitations in biocompatibility, biodegradability, and functionalization versatility. In this study, two porphyrin-free nanoscale covalent organic frameworks (nCOFs), TAPB-PDA and LZU-1, were evaluated as novel exogenous contrast agents for PAI. Their photoacoustic responses were systematically measured and compared with traditional contrast agents, such as gold nanoparticles (AuNPs) and ATTO532-labelled mesoporous silica nanoparticles. Experiments at 532 nm across a range of concentrations demonstrated strong photoacoustic signals from TAPB-PDA and LZU-1, with enhanced response at higher concentrations. Besides, both nCOFs also provided detectable signals at the NIR window at the lowest concentration, indicating a broad working range. A nonlinear model of the volume-integrated photoacoustic pressure is also provided. Furthermore, in vitro cytotoxicity assays indicated excellent nCOF biocompatibility, even at higher concentrations. Photostability tests under prolonged pulsed laser irradiation revealed that both nCOFs exhibit good resistance to photobleaching and partial signal recovery under intermittent excitation. Collectively, these findings highlight the potential of TAPB-PDA and LZU-1 nCOFs as biocompatible, biodegradable, and functionally versatile contrast agents for advanced photoacoustic imaging.