Fluorescence imaging in the second near-infrared window (NIR-II) is a new technique that permits visualization of deep anatomical features with unprecedented spatial resolution. Although attractive, effectively suppressing the interference signal of the background is still an enormous challenge for obtaining target-specific NIR-II imaging in the complex and dynamic physiological environment. Herein, dual-pathological-parameter cooperatively activatable NIR-II fluorescence nanoprobes (HISSNPs) are developed whereby hyaluronic acid chains and disulfide bonds act as the "double locks" to lock the fluorescence-quenched aggregation state of the NIR-II fluorescence dyes for performing ultrahigh specific imaging of tumors in vivo. The fluorescence can be lit up only when the "double locks" are opened by reacting with the "dual smart keys" (overexpressed hyaluronidase and thiols in tumor) simultaneously. In vivo NIR-II imaging shows that they reduce nonspecific activitation and achieve ultralow background fluorescence, which is 10.6-fold lower than single-parameter activatable probes (HINPs) in the liver at 15 h postinjection. Consequently, these "dual lock-and-key"-controlled HISSNPs exhibit fivefold higher tumor-to-normal tissue ratio than "single lock-and-key"-controlled HINPs at 24 h postinjection, attractively realizing ultrahigh specificity of tumor imaging. This is thought to be the first attempt at implementing ultralow background interference with the participation of multiple pathological parameters in NIR-II fluorescence imaging.

Enhancing the generation of reactive oxygen species (ROS) is an effective anticancer strategy. However, it is a great challenge to control the production and to image ROS in vivo, both of which are vital for improving the efficacy and accuracy of cancer therapy. Herein, an activatable semiconducting theranostic nanoparticle (NP) platform is developed that can simultaneously enhance ROS generation while self-monitoring its levels through ratiometric photoacoustic (PA) imaging. The NP platform can further guide in vivo therapeutic effect in tumors. The theranostic NP platform is composed of: (i) cisplatin prodrug and ferric ion catalyst for ROS generation, a part of combination cancer therapy; and (ii) a ratiometric PA imaging nanoprobe consisting of inert semiconducting perylene-diimide (PDI) and ROS activatable near-infrared dye (IR790s), used in ratiometric PA imaging of ROS during cancer treatment. Ratiometric PA signals are measured at two near-infrared excitation wavelengths: 680 and 790 nm for PDI and IR790s, respectively. The measurements show highly accurate visualization of OH generation in vivo. This novel ROS responsive organic theranostic NP allows not only synergistic cancer chemotherapy but also real-time monitoring of the therapeutic effect through ratiometric PA imaging.

J-aggregate nanoparticles (SQP-NPs(J)) were prepared for bright NIR-II fluorescence imaging guided photothermal therapy of cancer.

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A new class of small molecular NIR-II fluorophores based on aza-BODIPY with promising photophysical properties (large Stokes shift, superior photostability, good fluorescence brightness), show great potential as NIR-II in vivo imaging agents.