Enhanced NIR-II photoacoustic imaging performance of donor-acceptor semiconducting polymers enabled by donor conjugation extension

Abstract

Polymer-based photoacoustic imaging (PAI) in the second near-infrared window (NIR-II, 1000–1700 nm) has gained significant attention due to its unique advantages. However, the development of high-performance polymer contrast agents for NIR-II PAI still falls short of clinical needs, largely owing to a limited understanding of structure-property relationships. This study introduces a series of donor-acceptor (D-A) polymers PT-ATQ, PTT-ATQ, and PDTT-ATQ designed with progressively longer conjugated donor (D) units: thiophene (T), thieno[3,2-b]thiophene (TT), and dithieno[3,2-b:2′,3′-d]thiophene (DTT), aiming to understand the effects of conjugation extension in the D unit on PAI performance. Density functional theory (DFT) calculations showed that increasing the conjugation length enhances electron delocalization along the polymer backbone, boosting the conjugation effect and improving molecular coplanarity. Spectroscopic studies confirmed that this extension of conjugation and enhanced coplanarity significantly raised the absorption coefficient of the water-soluble nanoparticles PDTT-ATQ@NPs. Further results indicated that PDTT-ATQ@NPs not only exhibited excellent biocompatibility but also deliver superior in vitro PAI performance when irradiated with a 1064 nm pulsed laser. In vivo experiments in mice demonstrated a substantial increase in photoacoustic signal intensity, particularly in the ear (138.7-fold) and brain vasculature (64.8-fold), enabling the clear visualization of ear microvessels at 50 μm and brain microvessels at 100 μm. This research highlights the importance of conjugation length in the D unit for enhancing the PAI performance of D-A polymer contrast agents, offering crucial insights into the molecular design for future advancements in this field.