Traditional photodynamic therapy (PDT) is almost ineffective against deeply seated tumors due to the limited penetration depth of external light. The development of chemiexcited PDT is promising to address this issue, but it is still challenging to construct simple, efficient and targeted chemiexcited PDT systems. In this work, CPPO (bio(3,5,6-trichloro-2-n-pentyloxycarbonylphenyl) oxalate) and [Ru(phen)2(PIP-OCH3)](PF6)2 (Ru3, where phen = 1,10-phenanthroline, PIP-OCH3 = 2-(4-methoxy phenyl)-1Himidazo[4,5-f][1,10]phenanthroline) with efficient photo-catalytic NADH oxidation were co-encapsulated with DSPE-PEG 2000 to form Ru3/CPPO@PEG nanoparticles (NP3). Once internalized by cancer cells, Ru3 can be excited by the chemical energy produced by the reaction between CPPO and endogenous H2O2. The subsequent oxidation of intracellular NADH and generation of H2O2 in situ by excited Ru3 will further promote the sustained occurrence of chemical reaction, realizing a self-enhanced chemiexcited PDT. NP3 could effectively deplete intracellular NADH, inhibit ATP synthesis, increase H2O2 content, and produce reactive oxygen species (ROS) within cancer cells, thus exhibited efficient chemiexcited PDT activity against various cancer cells. Notably, minimal cytotoxicity was observed towards normal cells. Good therapeutic effects against subcutaneously implanted and lung metastatic tumors were also observed for NP3. The current findings may provide new sights for development of novel chemiexcited PDT.
(S)-3-chloro-1-phenyl-1-propanol ((S)-CPPO) is an important chiral intermediate predominantly used in the synthesis of the chiral side chain of (S)-fluoxetine. In this study, carbonyl reductase (CBR) from Novosphingobium aromaticivorans was successfully expressed in recombinant E. coli . The enzymatic activity of the recombinant CBR was significantly increased to 1875 U/mL in the fed-batch fermentation in a 10 L fermenter and recombinant CBR was then purified and characterized. By regenerating NADH with glucose dehydrogenase, 100 g/L 3-chloro-1-phenyl-1-propanone (3-CPP) was successfully converted to (S)-CPPO with a conversion of 100% and ee value of 99.6% after 12 h at 30 °C in PBS buffer (pH 7.0), which are the highest reported to date for the bio-production of (S)-CPPO and presented great potential for green production of (S)-CPPO at industrial scale.
Within the milieu of immune dysfunction, reactive oxygen species (ROS) play a pivotal role in inducing immunogenic cell death (ICD), countering the dysregulated tumor microenvironment. However, the administration of ROS at indiscriminate dosages may provoke deleterious immune responses. Therefore, precise regulation of ROS production is crucial to achieve efficacious therapeutic outcomes. We engineered an innovative afterglow nanosystem which is capable of real-time monitoring of ROS levels. Our findings reveal that Ru/CYQ@CPPO exhibits a markedly enhanced and prolonged afterglow luminescence, coupled with superior singlet oxygen (O2) generation, compared to the commercially available indocyanine green (ICG). In vitro studies demonstrated that Ru/CYQ@CPPO exhibits remarkable efficacy in photodynamic therapy (PDT) under irradiation at a wavelength of 450 nm. Furthermore, a significant correlation (R2 = 0.987) was observed between the intensity of afterglow luminescence and the rate of cancer cell inhibition.
危险品化学品经营许可证（带存储）