Migration from Lysosome to Nucleus: Monitoring Lysosomal Alkalization-Related Biological Processes with an Aminofluorene-Based Probe.

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

Rational Design of Polymethine Dyes with NIR-II Emission and High Photothermal Conversion Efficiency for Multimodal-Imaging-Guided Photo-Immunotherapy.

Phototheranostics have emerged and flourished as a promising pattern for cancer theranostics owing to their precise photoinduced diagnosis and therapeutic to meet the demands of precision medicine. The diagnosis information and therapeutic effect are directly determined by the fluorescence imaging ability and photothermal conversion efficiency (PCE) of phototheranostic agents. Hence, how to balance the competitive radiative and nonradiative processes of phototheranostic agents is the key factor to evaluate the phototheranostic effect. Herein, molecules named ICRs with high photostaibility  are rationally designed, exhibiting fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm) and high PCE, which are related to the strong donor-acceptor (D-A) interaction and high reorganization energy Noteworthily, ICR-Qu with stronger D-A interaction and a large-sized conjugated unit encapsulated in nanoparticles exhibits high PCE (81.1%). In addition, ICR-QuNPs are used for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to guide deep-tissue photonic hyperthermia, achieving precise removal and inhibition of breast cancer. Furthermore, combined with α-PD-1, ICR-QuNPs show huge potential to be a facile and efficient tool for photo-immunotherapy. More importantly, this study not only reports an "all-in-one" polymethine-based phototheranostic agent, but also sheds light on the exploration of versatile organic molecules for future practical applications.

[Molecular transport mechanism of pefloxacin mesylate binding with transferrin].

The binding mechanism between pefloxacin mesylate (PM) and transferrin (Tf) was explored using spectral experiment combined with molecular modeling techniques. The binding parameters and thermodynamic functions of PM-Tf solution system were measured at different temperatures. The effect of PM on molecular conformation of Tf was investigated and the interaction mechanism was also discussed. The results showed that dynamic quenching mechanism occurs with PM binding to Tf. The value of binding distances (r) is low, which indicates the occurrence of energy transfer. The drug had conformational effect on Tf, which resulted in changes of hydrophobic environment of the binding domain in Tf. According to the obtained thermodynamic parameters, the main interaction force between PM and Tf is attributed to hydrophobic bonding. The results of molecular modeling revealed that hydrophobic and hydrogen bonds are main binding forces in the PM-Tf system. These results were in accordance with spectral experiments. The research results have given a better theoretical reference for the study of pharmacological mechanism between protein and quinolone.