A step-by-step stimuli-response nanosystem that could be specifically activated by a “multistage rocket-like” process to improve its NIR-II/PA signals for imaging-guided photothermal/gas synergistic therapy.

cancer diagnosis including higher spatial and temporal resolution than the conventional NIR-I window fluorescence imaging (650-900 nm), mainly benefiting from the simultaneously suppressed tissue auto-fluorescence, photon scattering, and background interference. [3-5] In spite of significant improvements in NIR-II FL for imaging performance, accurate and wealthy information at different tissue penetration depths and scales cannot be effectively provided by a single imaging technology. [6,7] Magnetic resonance imaging (MRI) has outstanding performance in modern clinical medicine, offering higher spatial resolution than that of NIR-II FL. [8,9] Considering the desirable features of each imaging modality, integration of NIR-II FL and MRI may accurately delineate tumor by compensating their inherent limitations. Therefore, there is an urgent demand for an efficient imaging tool to achieve precise MRI/NIR-II FL dual-modal imaging of tumors. With the rapid development of biomedical engineering and nanotechnology, a variety of multimodal nanoprobes have been developed and provide accurate location and therapeutic improvement of tumor. [10-12] To date, most research has been focused on the rational design and fabrication of an all-in-one nanotheranostic as an extremely valuable strategy with multifunctional theranostic performance. [13,14] Wang and co-workers designed a novel small-molecule dye DPP-BT, which showed a single NIR laser triggered multifunctional properties for NIR-II fluorescence/photoacoustic (PA) Multi-modality cancer diagnosis techniques based on the second near-infrared window fluorescence (NIR-II FL, 1000-1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achieve theranostics is still a big challenge. Herein, a novel TME-activated nanosystem (FMSN-MnO 2-BCQ) employing degradable silica-based nanoplatform is designed, adjusting the ratio of intratumoral hydrogen peroxide (H 2 O 2)/glutathione (GSH) for magnetic resonance imaging (MRI)/NIR-II FL imaging and selfreinforcing chemodynamic therapy (CDT). Innovative bovine serum albumin (BSA)-modified fusiform-like mesoporous silica nanoparticles (FMSN) is fabricated as a carrier for NIR-II small molecule (CQ4T) and MRI reporter MnO 2. Remarkably, the BSA modification helped to achieve the dual-functions of high biocompatibility and enhance NIR-II fluorescence. The FMSN-MnO 2-BCQ with FMSN framework featuring a stepwise degradability in tumor interior released MnO 2 and BCQ nanoparticles. Through the specific degradation of MnO 2 by the TME, the produced Mn 2+ ions are effectively exerted Fenton-like activity to generate hydroxyl radical (•OH) from endogenous H 2 O 2 to eradicate tumor cells. More importantly, the GSH depletion due to the synergistic effect of tetrasulfide bond and MnO 2 in turn induced the oxidative cytotoxicity for self-reinforcing CDT.

In the second near‐infrared (NIR‐II) biowindow, multimodal optical imaging‐guided precise antitumor therapy is a novel strategy for high‐efficiency tumor theranostics, however, the all‐in‐one dual NIR‐II photoacoustic (NIR‐II PA) and NIR‐II fluorescence (NIR‐II FL) nanoprobes have been rarely reported mainly due to the short of a simple and universal design approach. Herein, a NIR‐II PA/NIR‐II FL imaging‐adjustable nanozyme (HSC‐2) is designed and developed to guide precise photothermal‐catalytic synergistic therapy. Based on the ionic liquids adsorption capacity, the electronic structure of zeolite nano‐Beta (three dimensional 12‐ring pore system and large surface area) can be turned from the indirect band gap to direct band gap via doping carbon in the framework, resulting in outstanding NIR‐II FL emission characteristics. As the silicon etching reaction proceeds, HSC‐2 shows superior dual‐modal NIR‐II PA/NIR‐II FL imaging performance facilitated by the optimal silicon‐to‐carbon ratio, simultaneously ensuring efficient tumor photothermal therapy (PTT) in the NIR‐II window. Impressively, the peroxidase‐mimic activity of HSC‐2 in the tumor microenvironment could be further remarkably enhanced by its photothermal effect, leading to excellent synergistic PTT/catalytic therapy. Moreover, the HSC‐2 exhibits dual‐enzyme activity, and its catalase‐like property could effectively eliminate excessive ROS for protection of the normal cells.

Although nanomedicine has shown high performance in tumor theranostics, the anticancer activity is still limited by the drug delivery performance, especially lack of targeting capability, poor tumor accumulation, and insufficient...