pH-responsive dynamically cross-linked nanogels with effective endo-lysosomal escape for synergetic cancer therapy based on intracellular co-delivery of photosensitizers and proteins.

Co-delivery of photosensitizers (PSs) and protein drugs represents great potentiality for enhancing the efficiency of synergistic cancer therapy. However, the intricate tumor-microenvironment and the lack of nanoplatforms to co-deliver both into cancer cells and activate their functions significantly hinder the clinical translation of this combined approach for cancer treatment. Herein, a chlorine e6 (Ce6)-functionalized and pH-responsive dynamically cross-linked nanogel (Ce6@NG) is fabricated by formation of benzoic imine linkages between Ce6-modified methoxy poly (ethyleneglycol)-block-poly (diethylenetriamine)-L-glutamate-Ce6 [MPEG-b-P(Deta)LG-Ce6] and terephthalaldehyde as cross-linkers for effective intracellular co-delivery of Ce6 and cytochrome c (CC), which could form a novel combination therapy system (CC/Ce6@NGs). The pH-sensitive benzoic imine bonds in the CC/Ce6@NGs endow them with excellent systemic stability under normal physiological environment while this nanosystem can be further cationized to enhance cell uptake in acidic extracellular environment. Upon cellular internalization, CC/Ce6@NGs can rapidly escape from the endo/lysosomal compartments and subsequently activate Ce6 to generate cytotoxic singlet oxygen upon laser irradiation and release of CC to induce programmed cell death by complete cleavage of benzoic imines at more acidic intracellular environments. Importantly, the catalase-like activity of CC can decompose H2O2 to produce O2 for hypoxia alleviation and improvement of the photodynamic therapy (PDT) of cancer. Moreover, this enhanced synergistic anticancer activity is confirmed both in vitro and in vivo. In view of the versatile chemical conjugation, this research offers a promising and smart nanosystem for intracellular co-delivery of PSs and therapeutic proteins.

[The Study of Three-Dimensional Synchronous Fluorescence Spectral Characteristics of Liuwei Dihuang Pills].

Three-dimensional synchronous fluorescence of each component of Liuwei dihuang pills (Prepared rehmannia root, cornel, yam, alisma, poria cocos, and cortex moutan) is measured by using FLS920P fluorescence spectrometer. Feature parameters were extracted. It can be found that each component is fluorescent material and the lines are all different. Furthermore, Three-dimensional synchronous fluorescence of Liuwei dihuang pills boiling with standard water and non-standard water are all measured and there are significant differences between them. It can be applied in distinguishing different formula of Chinese medicine decoction. Experimental and Theoretical conclusion show that: the three-dimensional fluorescence spectrometry method and the combination of synchronous fluorescence spectroscopy method can further improve the sensitivity and selectivity of fluorescence spectroscopy, have a distinct advantage in a complex multi-component mixture of fluorescence spectroscopic analysis. The study can provide a convenient and reliable method for establishing a complete fingerprint of Chinese traditional medicine. It also can help identifying the component and the quality of Chinese patent medicine.

[Identification of Prepared Rehmannia Root in Different Regions by Using Derivative Synchronous Fluorescence Spectrum].

Three-dimensional synchronous fluorescence spectrum of prepared rehmannia root from different regions were measured and feature parameters were extracted. It can be found that the effective fluorescent compositions of prepared rehmannia root from different regions are similar. The relationships between the spectrum-effect were established. This study can provide reference for clinicaldosage. First order derivative and second order derivative of prepared rehmanniaroot from different regions can be got by programming respectively. Magnifing synchronous emission spectrum of the shoulder strap, the subtle differences of the spectrum can be distinguished and the method, derivative synchronous fluorescence spectrum, to identify different regions of prepared rehmannia root are acquired.