Coupling Nanoscale Precision with Multiscale Imaging: A Multifunctional Near-Infrared Dye for the Brain.

Live imaging of primary neural cells is crucial for monitoring neuronal activity, especially multiscale and multifunctional imaging that offers excellent biocompatibility. Multiscale imaging can provide insights into cellular structure and function from the nanoscale to the millimeter scale. Multifunctional imaging can monitor different activities in the brain. However, this remains a challenge because of the lack of dyes with a high signal-to-background ratio, water solubility, and multiscale and multifunctional imaging capabilities. In this study, we present a neural dye with near-infrared (NIR) emissions (>700 nm) that enables ultrafast staining (in less than 1 min) for the imaging of primary neurons. This dye not only enables multiscale neural live-cell imaging from vesicles in neurites, neural membranes, and single neurons to the whole brain but also facilitates multifunctional imaging, such as the monitoring and quantifying of synaptic vesicles and the changes in membrane potential. We also explore the potential of this NIR neural dye for staining brain slices and live brains. The NIR neural dye exhibits superior binding with neural membranes compared to commercial dyes, thereby achieving multiscale and multifunctional brain neuroimaging. In conclusion, our findings introduce a significant breakthrough in neuroimaging dyes by developing a category of small molecular dyes.

Fast Delivery of Multifunctional NIR-II Theranostic Nanoaggregates Enabled by the Photoinduced Thermoacoustic Process.

Multifunctional nanoaggregates are widely used in cancer phototheranostics. However, it is challenging to construct their multifunctionality with a single component, and deliver them rapidly and efficiently without complex modifications. Herein, a NIR-absorbing small molecule named TBT-2(TP-DPA) is designed and certify its theranostic potentials. Then, their nanoaggregates, which are simply encapsulated by DSPE-PEG, demonstrate a photothermal efficiency of 51% while keeping a high photoluminescence quantum yield in the NIR region. Moreover, the nanoaggregates can be excited and delivered by an 808 nm pulse laser to solid tumors within only 40 min. The delivery efficiency and theranostic efficacy are better than that of the traditional enhanced permeability and retention (EPR) effect (generally longer than 24 hours). This platform is first termed as the photoinduced thermoacoustic (PTA) process, and confirm its application requires both NIR-responsive materials and pulse laser irradiation. This study not only inspires the design of multifunctional nanoaggregates, but also offers a feasible approach to their fast delivery. The platform reported here provides a promising prospect to boost the development of multifunctional theranostic drugs and maximize the efficacy of used medicines for their clinical applications.

Side-Chain-Tuned Molecular Packing Allows Concurrently Boosted Photoacoustic Imaging and NIR-II Fluorescence.

It is generally considered that photoacoustic imaging (PAI) and fluorescence imaging (FLI) cannot be enhanced concurrently, as they are dependent on competitive photophysical processes at the single-molecule level. Herein, we reveal that BDTR9-OC8 and BDTR9-C8, which have identical π-conjugated backbones but are substituted by side chains of different rigidity, show distinct phototheranostic properties in the aggregated state. The NIR-II FLI and PAI brightness of BDTR9-C8 nanoparticles are enhanced by 4.6 and 1.4 times compared with BDTR9-OC8 nanoparticles. Theoretical calculations and GIWAXS analysis revealed that BDTR9-C8 with rigid side chains shows a relative amorphous condensed state, which will benefit the efficient transportation of photo-generated excitons and phonons, subsequently enhancing the FLI and PAI signals. Besides, both nanoparticles exhibit excellent photothermal conversion efficiency due to their strong light-harvesting capability and are considered effective photothermal therapy materials. This work provides an illuminating strategy for material design in the future.

A Multispectral Photoacoustic Tracking Strategy for Wide-Field and Real-Time Monitoring of Macrophages in Inflammation.

Inflammation is a common defensive response of the vascular system that involves the activation and mediation of immune cell and stem cell homing. However, it is usually hard to track and analyze the real-time status of these cell types toward the inflammation microenvironment in a large field of view with desired resolution. Here, we designed and synthesized near-infrared absorbing semiconducting polymer nanoparticles, BBT-TQP-NP (BTNPs), as the cell tracker and utilized their photoacoustic activity to unveil the targeting behaviors of macrophages, neutrophils, and mesenchymal stem cells to the inflamed sites in mice. Facilitated by multispectral optical-resolution photoacoustic microscopy (ORPAM), we can continuously monitor the in vivo photoacoustic signals of the labeled cells with cellular resolution in a wide-field (a circle field-of-view with a diameter of 9 mm). In addition, the highly sensitive observation of vascular microstructures and labeled cells can reveal the time-dependent accumulating behaviors of various cell types toward inflammation sites. As a result, our study offers an effective and promising tracking strategy to analyze the in vivo status and fate of functional cells in targeting the diseased/damaged regions.