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Photodynamic therapy (PDT) could induce apoptosis by releasing reactive oxygen species (ROS) to treat tumor. Application of pH/light dual-activated nanoparticles could generate ROS in the acidic tumor microenvironment under 808 nm laser irradiation for precise treatment. L-arginine (L-Arg) triggered by ROS is an efficient nitric oxide (NO) donor for gas therapy. In addition, it is reported that peroxynitrite (ONOO-) produced by rapid reaction of ROS and NO could sensitize PDT and induce apoptosis for synergistic treatment. Herein, we developed the L-Arg loaded pH/light dual-activated PEGylated photosensitizer for self-assembly into nanoparticles named Rho-Arg. As measured by fluorescence spectroscopy, the pKa of Rho-Arg was 5.5, which is suitable for applying in the tumor microenvironment. The nanoplatform was firstly activated under the acidic condition of tumor, and then illuminated by 808 nm laser to controllably release ROS, and sequentially produced NO and ONOO-. In conclusion, the Rho-Arg nanoplatform may provide a promising synergistic therapy tool for tumor treatment. • "Dual lock" control enables effective precision treatment. • An excellent nitric oxide donor. • Photodynamic therapy combined with gas therapy for tumor suppression. • Quickly generate ONOO- sensitized photodynamic therapy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether hydrogen sulfide provide protective effects on atmosphere particulate matter (PM)-induced emphysema and airway inflammation and its mechanism. Methods: Wild type C57BL/6 and Nrf2 knockout mice were exposed to PM (200 µ g per mouse). Hydrogen sulfide or propargylglycine were administered by intraperitoneal injection respectively 30 min before PM exposure, mice were anesthetized 29th day after administration. Mice emphysema, airway inflammation, and oxidative stress were evaluated, the expression of NLRP3, active caspase-1, and active caspase-3 were detected. Alveolar epithelial A549 cells line were transfected with control small interfering RNA (siRNA) or Nrf2 siRNA and then incubated with or without hydrogen sulfide for 30 min before exposed to fine particulate matter for 24 h, cell viability, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling (TUNEL) assay, the secretion of interleukin (IL)-1 β , ASC speck formation, the expression level of NLRP3, active caspase-1, and active caspase-3 were measured. Results: PM significantly increased mice emphysema and airway inflammation measured by mean linear intercept, alveolar destroy index and total cell, neutrophil counts, cytokines IL-6, tumor necrosis factor (TNF)- α , CXCL1, IL-1 β in bronchoalveolar lavage fluid. PM-induced mice emphysema and airway inflammation was greatly attenuated by hydrogen sulfide, while propargylglycine aggravated that. PM-induced oxidative stress was reduced by hydrogen sulfide as evaluated by 8-OHdG concentrations in lung tissues. The expression of NLRP3, active caspase-1, and active caspase-3 enhanced by PM were also downregulated by hydrogen sulfide in mice lung. The protective effect of hydrogen sulfide on emphysema, airway inflammation, inhibiting oxidative stress, NLRP3 inflammasome formation, and anti-apoptosis was inhibited by Nrf2 knockout in mice. Similarly, hydrogen sulfide attenuated the secretion of IL-1 β , NLRP3 expression, caspase-1 activation, ASC speck formation, and apoptosis caused by fine particulate matter exposure in A549 cells but not in Nrf2 silenced cells. Conclusion: Hydrogen sulfide played a protect role in PM-induced mice emphysema and airway inflammation by inhibiting NLRP3 inflammasome formation and apoptosis via Nrf2-dependent pathway. [ABSTRACT FROM AUTHOR]

The antibiotic therapy usually leads to the bacterial resistance, and the traditional photosensitizer was in "always on" state with damage to normal tissue. Fortunately, the activatable near-infrared photosensitizer has a high depth of tissue penetration, and can be specifically released with low side effect. Therefore, we designed and synthesized a penicillin G acylase (PGA) activable photosensitizer (NFh-PGA), which could be activated to produce NFh-OH. NFh-OH can product singlet oxygen (1O 2) under near-infrared light 730 nm excitation, and have an excellent antibacterial effect in vitro and in vivo. The probe accelerates the healing of bacterial infection wounds by near-infrared imaging guiding PDT. This work provides a strategy for the integrated design of diagnosis and treatment of bacterial infection. [Display omitted] ● A novel activable photosensitizer (NFh-PGA) by PGA was developed. ● The fluorescence and phototherapeutic ability of the probe kept the OFF state in the normal physiological environment. ● The NFh-PGA could be specifically activated and efficiently generating singlet oxygen (1O 2) under 730 nm laser. ● The NFh-PGA played an excellent bactericidal effect and accelerated the healing speed of infected wounds. [ABSTRACT FROM AUTHOR]

Phototherapy has developed as a powerful method for remedial modalities. The conventional photosensitizers are "always on" state and lack tumor targeting, which contributed to poor therapeutic effect and high toxicity. Therefore, we developed an aspartyl aminopeptidase (DNPEP) activated self-assembled organic nanoparticles (NRh-Asp NPs) with sensitive external irradiation-induced photothermal therapy and photodynamic therapy (PTT/PDT). NRh-Asp NPs can be activated to NRh–NH 2 NPs by DNPEP, demonstrating strong near-infrared (NIR) fluorescence, and efficiently generating heat and singlet oxygen under the near-infrared laser. NRh-Asp NPs was successfully used for visualizing DNPEP in vitro and in vivo in NIR region, and demonstrated good synergistic anti-cancer efficacy of PDT and PTT. These results suggest that DNPEP-mediated NRh-Asp NPs are promising candidates for image-guided phototherapeutic of tumor. [Display omitted] • A novel self-assembled fluorescent probe (NRh-Asp NPs) was developed for detecting DNPEP activity and phototherapeutic therapy of tumor. • The NRh-Asp NPs exhibited high selectivity/sensitivity for DNPEP analysis with NIR fluorescent. • The fluorescence and phototherapeutic ability (PTT and PDT) of NRh-Asp NPs kept only the ON state in the tumor microenvironment. • The NRh-Asp NPs can effectively inhibit tumor growth by synergistic effects of PTT and PDT without causing damage to other organs. [ABSTRACT FROM AUTHOR]