Regio-isomerization boosts NIR-II photothermal conversion and multimodal imaging in conjugated polymer nanoparticles for effective cancer therapy.

Abstract

Second near-infrared (NIR-II) photoacoustic imaging (PAI) and fluorescence imaging (FLI) have emerged as powerful tools for deep-tissue visualization, yet most organic probes remain limited to single imaging modality and lack therapeutic functions. Here, we report a regio-isomerization strategy to construct NIR-II-absorbing conjugated polymer nanoparticles (BDTCP3 NPs and BDTCP2 NPs) that integrate high-contrast NIR-II PAI/FLI and efficient photothermal conversion within a single polymeric platform. By controlling the conjugation site of the thiophene moiety on the donor-acceptor polymer backbone, BDTCP3 NPs exhibit a twisted conformation with suppressed intermolecular π-π stacking, as confirmed by density functional theory calculations, reorganization energy analyses and GIWAXS measurements. This molecular design affords BDTCP3 NPs with a large Stokes shift (214 nm), high NIR-II emission, and an impressive photothermal conversion efficiency of 65% under 1064 nm laser irradiation. Upon intravenous administration, BDTCP3 NPs enable high-resolution NIR-II PAI and fluorescence angiography, robust NIR-II PAI/FLI/photothermal trimodal imaging of tumors, and effective photothermal ablation of 4T1 tumors in live mice under low-power 1064 nm laser irradiation (0.5 W cm-2), achieving tumor regression without detectable systemic toxicity. This work establishes regio-isomerization as a powerful molecular design paradigm for developing high-performance NIR-II organic phototheranostic agents, opening new avenues for multimodal imaging-guided cancer therapy.