ABSTRACT
Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O2) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.
ABSTRACT
Wastewater from high-speed railway trains represents a mobile reservoir of microorganisms with antibiotic resistance. It harbors abundant and diverse antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). This study investigated the removal of ARB and ARGs in a pilot-scale reactor, which consisted of an anaerobic/anoxic/oxic process, anaerobic/anoxic/aerobic process, and ozone-based disinfection to treat 1 m3/day wastewater from an electric multiple unit high-speed train. Further, the high prevalence of two mobile genetic elements (intI1 and Tn916/615) and five ARGs (tetA, tetG, qnrA, qnrS, blaNDM-1, and ermF) was investigated using quantitative PCR. Significant positive correlations between ARGs (tetA, blaNDM-1, and qnrA) and intI1 were identified (R2 of 0.94, 0.85, and 0.70, respectively, P < 0.01). Biological treatment could significantly reduce Tn916/1545 (2.57 logs reduction) and Enterococci (2.56 logs reduction of colony forming unit (CFU)/mL), but the qnrS abundance increased (1.19 logs increase). Ozonation disinfection could further significantly decrease ARGs and Enterococci in wastewater, with a reduction of 1.67-2.49 logs and 3.16 logs CFU/mL, respectively. Moreover, food-related bacteria families which may contain opportunistic or parasitic pathogens (e.g., Moraxellaceae, Carnobacteriaceae, and Ruminococcaceae) were detected frequently. Enterococci filtered in this study shows multi-antibiotic resistance. Our study highlights the significance to mitigate antibiotic resistance from wastewater generated from high-speed railway trains, as a mobile source.
