Acceptor engineering of small-molecule fluorophores for NIR-II fluorescence and photoacoustic imaging.

Fluorescence imaging in the second near-infrared window (NIR-II) has been an emerging technique in diverse in vivo applications with high sensitivity/resolution and deep tissue penetration. To date, the design principle of the reported NIR-II organic fluorophores has heavily relied on benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBTD) as a strong electron acceptor. Here, we report the rational design and synthesis of a NIR-II fluorescent molecule with the rarely used [1,2,5]thiadiazolo[3,4-f]benzotriazole (TBZ) core to replace BBTD as the electron acceptor. Thanks to the weaker electron deficiency of the TBZ core than BBTD, the newly yielded NIR-II molecule (BTB) based nanoparticles have a higher mass extinction coefficient and quantum yield in water. In contrast, the nanoparticle suspension of its counterpart with BBTD as the core is nearly nonemissive. The NIR-II BTB nanoparticles allow video-rate fluorescence imaging for vasculature imaging in ears, hindlimbs, and the brain of the mouse. Additionally, its large absorptivity in the NIR-I region also promotes bioimaging using photoacoustic microscopy (PAM) and tomography (PAT). Upon surface conjugation with the Arg-Gly-Asp (RGD) peptide, the functionalized nanoparticles ensured targeted detection of integrin-overexpressed tumors through both imaging modalities in two- and three-dimensional views. Thus, our approach to engineering acceptors of organic fluorophores offers a promising molecular design strategy to afford new NIR-II fluorophores for versatile biomedical imaging applications.

Photoacoustic and Magnetic Resonance Imaging Bimodal Contrast Agent Displaying Amplified Photoacoustic Signal.

Progress in photoacoustic (PA) and magnetic resonance imaging (MRI) bimodal contrast agents has been achieved mainly by utilizing the imaging capability of single or multiple components and consequently realizing the desired application for both imaging modalities. However, the mechanism of the mutual influence between components within a single nanoformulation, which is the key to developing high-performance multimodal contrast agents, has yet to be fully understood. Herein, by integrating conjugated polymers (CPs) with iron oxide (IO) nanoparticles using an amphiphilic polymer, a bimodal contrast agent named CP-IO is developed, displaying 45% amplified PA signal intensity as compared to bare CP nanoparticle, while the performance of MRI is not affected. Further experimental and theoretical simulation results reveal that the addition of IO nanoparticles in CP-IO nanocomposites contributes to this PA signal amplification through a synergistic effect of additional heat generation and faster heat dissipation. Besides, the feasibility of CP-IO nanocomposites acting as PA-MRI bimodal contrast agents is validated through in vivo tumor imaging using mice models. From this study, it is demonstrated that a delicately designed structural arrangement of various components in a contrast agent could potentially lead to a superior performance in the imaging capability.

Bright Aggregation-Induced-Emission Dots for Targeted Synergetic NIR-II Fluorescence and NIR-I Photoacoustic Imaging of Orthotopic Brain Tumors.

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-1 cm-1 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.