Precise diagnostics are of significant importance to the optimal treatment outcomes of patients bearing brain tumors. NIR-II fluorescence imaging holds great promise for brain-tumor diagnostics with deep penetration and high sensitivity. This requires the development of organic NIR-II fluorescent agents with high quantum yield (QY), which is difficult to achieve. Herein, the design and synthesis of a new NIR-II fluorescent molecule with aggregation-induced-emission (AIE) characteristics is reported for orthotopic brain-tumor imaging. Encapsulation of the molecule in a polymer matrix yields AIE dots showing a very high QY of 6.2% with a large absorptivity of 10.2 L g cm at 740 nm and an emission maximum near 1000 nm. Further decoration of the AIE dots with c-RGD yields targeted AIE dots, which afford specific and selective tumor uptake, with a high signal/background ratio of 4.4 and resolution up to 38 µm. The large NIR absorptivity of the AIE dots facilitates NIR-I photoacoustic imaging with intrinsically deeper penetration than NIR-II fluorescence imaging and, more importantly, precise tumor-depth detection through intact scalp and skull. This research demonstrates the promise of NIR-II AIE molecules and their dots in dual NIR-II fluorescence and NIR-I photoacoustic imaging for precise brain cancer diagnostics.

simultaneously achieve high contrast, good spatiotemporal resolution, deep penetration, and good sensitivity. [7][8][9][10] Although conventional in vivo NIR-I brain fluorescence imaging has advantages in high sensitivity, good temporal resolution, and real-time wide-field image, it suffers from low penetration, non-negligible autofluorescence, and scattering-limited spatial resolution. [7,11] On the other hand, brain photoacoustic (PA) imaging (PAI) with reconstruction of acoustic waves generated by light absorbers after pulsed NIR laser illumination has demonstrated good ultrasonic spatial resolution, and much deeper penetration than fluorescence imaging, because ultrasound attenuates far less than light in vivo. [12] However, conventional PAI often shows severe background interference owing to the negligible tissue absorbance within NIR-I region. [9,12] In addition, multimodal brain imaging with combined desirable features of different imaging modalities could overcome shortcomings of single modality and improve diagnostic accuracy. [2,8,9,13] So far, multimodal imaging generally requires administration of different contrast agents or nanoparticles (NPs) containing multiple components, [2,8,13] which faces the challenges of different location for the former and low NP reproducibility for the latter. It is Diagnostics of cerebrovascular structures and microscopic tumors with intact blood-brain barrier (BBB) significantly contributes to timely treatment of patients bearing neurological diseases. Dual NIR-II fluorescence and photoacoustic imaging (PAI) is expected to offer powerful strength, including good spatiotemporal resolution, deep penetration, and large signal-to-background ratio (SBR) for precise brain diagnostics. Herein, biocompatible and photostable conjugated polymer nanoparticles (CP NPs) are reported for dualmodality brain imaging in the NIR-II window. Uniform CP NPs with a size of 50 nm are fabricated from microfluidics devices, which show an emission peak at 1156 nm with a large absorptivity of 35.2 L g −1 cm −1 at 1000 nm. The NIR-II fluorescence imaging resolves hemodynamics and cerebral vasculatures with a spatial resolution of 23 µm at a depth of 600 µm. The NIR-II PAI enables successful noninvasive mapping of deep microscopic brain tumors (<2 mm at a depth of 2.4 mm beneath dense skull and scalp) with an SBR of 7.2 after focused ultrasound-induced BBB opening. This study demonstrates that CP NPs are promising contrast agents for brain diagnostics. Brain ImagingClear pinpointing of cerebral vasculature and tumor structures with different morphologies and biology characteristics in complex central neural system significantly benefits patients bearing brain pathologies like neurological disorder, traumatic injury, stroke, Alzheimer's disease, and even early-and late-stage tumors. [1][2][3][4][5][6][7][8][9] Conventional neuroimaging modalities exhibit certain intrinsic limitations in each modality, which could not

NIR II conjugated polymer nanoparticles with good biocompatibility, excellent photoacoustic stability and high imaging contrast are formulated, which allows highly efficient imaging of orthotopic brain tumors with a high signal/background ratio and a good penetration depth.

Exogenous contrast‐agent‐assisted NIR‐II optical‐resolution photoacoustic microscopy imaging (ORPAMI) holds promise to decipher wide‐field 3D biological structures with deep penetration, large signal‐to‐background ratio (SBR), and high maximum imaging depth to depth resolution ratio. Herein, NIR‐II conjugated polymer nanoparticle (CP NP) assisted ORPAMI is reported for pinpointing cerebral and tumor vasculatures. The CP NPs exhibit a large extinction coefficient of 48.1 L g−1 at the absorption maximum of 1161 nm, with an ultrahigh PA sensitivity up to 2 µg mL−1. 3D ORPAMI of wide‐field mice ear allows clear visualization of regular vasculatures with a resolution of 19.2 µm and an SBR of 29.3 dB at the maximal imaging depth of 539 µm. The margin of ear tumor composed of torsional dense vessels among surrounding normal regular vessels can be clearly delineated via 3D angiography. In addition, 3D whole‐cortex cerebral vasculatures with large imaging area (48 mm2), good resolution (25.4 µm), and high SBR (22.3 dB) at a depth up to 1001 µm are clearly resolved through the intact skull. These results are superior to the recently reported 3D NIR‐II fluorescence confocal vascular imaging, which opens up new opportunities for NIR‐II CP‐NP‐assisted ORPAMI in various biomedical applications.

Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor-acceptor (D-A) structured porphyrin-containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D-A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state-of-art porphyrin-based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 × 10 m cm at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer-based photothermal therapeutic materials for potential personalized theranostic nanomedicine.