1169945-44-1Relevant articles and documents
Peroxynitrite Activatable NIR-II Fluorescent Molecular Probe for Drug-Induced Hepatotoxicity Monitoring
Li, Dandan,Wang, Shangfeng,Lei, Zuhai,Sun, Caixia,El-Toni, Ahmed Mohamed,Alhoshan, Mansour Saleh,Fan, Yong,Zhang, Fan
, p. 4771 - 4779 (2019)
Drug-induced hepatotoxicity represents an important challenge for safety in drug development. The production of peroxynitrite (ONOO-) is proposed as an early sign in the progression of drug-induced hepatotoxicity. Currently, reported ONOO- probes mainly emit in the visible range or the first NIR window, which have limited in vivo biosensing application due to the autofluorescence and photon scattering. Herein, we developed a peroxynitrite activatable second near-infrared window (NIR-II) molecular probe for drug-induced hepatotoxicity monitoring, based on the fusion of an NIR-II fluorescence turn-on benzothiopyrylium cyanines skeleton and the phenyl borate. In the presence of ONOO-, the probe IRBTP-B can turn on its NIR-II fluorescence by yielding its fluorophore IRBTP-O and display good linear response to ONOO-. Tissue phantom study confirmed reliable activated signals could be acquired at a penetration depth up to 5 mm. Using this probe, we disclose the upregulation of ONOO- in a preclinical drug-induced liver injury model and the remediation with N-acetyl cysteine (NAC) in vivo. We expect that this strategy will serve as a general method for the development of an activatable NIR-II probe based on the hydroxyl functionalized reactive sites by analyte-specific triggering.
Oxidation-responsive poly(amino ester)s containing arylboronic ester and self-immolative motif: Synthesis and degradation study
Song, Cheng-Cheng,Ji, Ran,Du, Fu-Sheng,Li, Zi-Chen
, p. 8416 - 8425 (2013/12/04)
We report the synthesis of a new type of amphiphilic poly(amino ester)s which can be completely degraded in aqueous media via H2O2 oxidation. The polymers were prepared by the controlled Michael-type addition polymerization of a phenylboronic pinacol ester-containing diacrylate and N-aminoethylpiperazine, followed by postmodification with mPEG5K-succinimide ester. Upon oxidation, the side chain phenylboronic esters will be transformed into phenol groups which can trigger the sequential self-immolative process to degrade the polymer main chain. Meanwhile, the amino groups on the polymer main chain are capable of trapping the highly active quinone methides generated in situ during the oxidative degradation of the polymers. Based on the detailed oxidation kinetics and products of several model compounds, the H 2O2-triggered degradation of nanoparticles of these copolymers was investigated by NMR spectroscopy, GPC, and Nile red fluorescence probe. The results demonstrate that the poly(amino ester) backbones were completely degraded by H2O2, resulting in the dissociation of nanoparticles. Oxidative degradation rates of the nanoparticles could be accelerated by increasing the concentration of H2O2, the PEGylation degree, or the pH of the buffer. Interestingly, the in situ formed quinone methides could be captured by secondary amines due to their higher nucleophilicity than H2O. Of potential importance, these amphiphilic oxidation-responsive copolymers are sensitive to stimulation of 200 μM H 2O2; therefore, they may find application in the field of intelligent drug/gene delivery systems.
