All-in-One Zeolite-Carbon-Based Nanotheranostics with Adjustable NIR-II Window Photoacoustic/Fluorescence Imaging Performance for Precise NIR-II Photothermal-Synergized Catalytic Antitumor Therapy.

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.

Hollow carbon-based nanosystem for photoacoustic imaging-guided hydrogenothermal therapy in the second near-infrared window.

Compared with the near-infrared-I spectral window (NIR-I, 650-950 nm), a newly developed imaging and treatment window with a 1000-1700 nm range (defined as the NIR-II bio-window) has attracted much attention owing to its higher spatiotemporal resolution, increased tissue penetration depth and therapeutic efficacy. Herein, we designed a nanotheranostic platform (HC-AB NPs) via loading ammonia borane (AB) into hollow carbon nanoparticles (HCs) for NIR-II photoacoustic (PA) imaging-guided NIR-II hydrogenothermal therapy. Importantly, by exploiting the characteristics of beta zeolite as a hard template and a template-carbonization-corrosion process, the prepared HCs have excellent NIR-II absorption performance and AB loading capacity. With the high biocompatibility of HC-AB NPs, an efficient synergistic anti-tumor strategy has been achieved via high intratumoural accumulation and acid-stimulated H2 release as well as PA-guided precise NIR-II photothermal therapy. The HC-AB NPs as a promising nanotheranostic platform opens a new avenue for high-efficacy NIR-II hydrogenothermal therapy.

Biodegradable Multifunctional Nanotheranostic Based on Ag2S-Doped Hollow BSA-SiO2 for Enhancing ROS-Feedback Synergistic Antitumor Therapy.

Stimuli-responsive silica nanoparticles are an attractive therapeutic agent for effective tumor ablation, but the responsiveness of silica nanoagents is limited by intrastimulation level and silica framework structure. Herein, a biodegradable hollow SiO2-based nanosystem (Ag2S-GOx@BHS NYs) is developed by a novel one-step dual-template (bovine serum albumin (BSA) and cetyltrimethylammonium bromide (CTAB)) synthetic strategy for image-guided therapy. The Ag2S-GOx@BHS NYs can be specifically activated in the tumor microenvironment via a self-feedback mechanism to achieve reactive oxygen species (ROS)-induced multistep therapy. In response to the inherent acidity and H2O2 at the tumor sites, Ag2S-GOx@BHS would accelerate the structural degradation while releasing glucose oxidase (GOx), which could efficiently deplete intratumoral glucose to copious amounts of gluconic acid and H2O2. More importantly, the sufficient H2O2 not only acts as a reactant to generate Ag+ from Ag2S for metal-ion therapy and improves the oxidative stress but also combines with gluconic acid results in the self-accelerating degradation process. Moreover, the released Ag2S nanoparticles can help the Ag2S-GOx@BHS NYs realize the second near-infrared window fluorescence (NIR-II FL) and photoacoustic (PA) imaging-guided precise photothermal therapy (PTT). Taken together, the development of a self-feedback nanosystem may open up a new dimension for a highly effective multistep tumor therapy.

Paeonol prevents lipid metabolism dysfunction in palmitic acid-induced HepG2 injury through promoting SIRT1-FoxO1-ATG14-dependent autophagy.

This study aimed to investigate the effects of paeonol (Pae) on lipid metabolism in palmitic acid (PA)-induced injury of HepG2, and to evaluate the protective mechanisms. Lipid metabolism dysfunction of HepG2 cells was produced by administration of palmitic acid (PA). The cells were pretreated with different concentrations of Pae. MTT method was used to detect the cell survival; lipid metabolism was evaluated based on total cholesterol (TC), triglycerides (TG); Western blotting was used to detect the expression of Sirtuin 1 (SIRT1), autophagy related 14 (ATG14), microtubule-associated protein 1A/1B-light chain 3 (LC3) and p62 proteins; immunoprecipitation was used to detect the expression of acetylated FoxO1. After treatment for 24 h, the inhibitory concentration 50 (IC50) of PA in HepG2 cells was about 566.8 µM. Pae at the concentration range from 7.5 to 30 µM did not affect cell viability. Thus, 500 µM PA was used to model metabolism dysfunction and Pae at the concentration range was selected to investigate the protective effect. Compared with the normal control group, the cell survival rate decreased, the number of lipid droplets, and TC and TG levels increased in the model group. Compared with model group, the cell survival rate of Pae (7.5, 15, 30 µM) group increased, the number of lipid droplets and content of TC and TG decreased, the ratio of LC3-II/I increased and p62 expression decreased with pretreatment of Pae. Additionally, Pae pretreatment promoted SIRT1 and ATG14 expression, but reduced acetylated FoxO1 levels in PA-treated cells. Most importantly, autophagy inhibitor, as well as SIRT1 inhibitor blocked the effects of Pae on PA-induced cell injury and metabolism dysfunction, respectively. Pae prevents lipid metabolism dysfunction in PA-induced HepG2 injury by promoting SIRT1-FoxO1-ATG14-dependent autophagy.