The multifaceted roles of peptides in "always-on" near-infrared fluorescent probes for tumor imaging.

Tumor-targeted near-infrared (NIR) fluorescence imaging by using NIR fluorescent probes has attracted extensive attentions in the field of tumor imaging and is becoming an attractive strategy for early cancer diagnosis and surgical guidance for the past few decades. Especially, due to the high affinity and low toxicity, the peptide-based NIR fluorescent probes play an important role in the field of tumor-targeted imaging and therapy. Extensive attempts have been made to develop a set of nontoxic and efficacious "always-on" peptide-based NIR fluorescent probes. In this review, we give a comprehensive analysis of the "always-on" peptide-based NIR fluorescent probes for tumor-targeting for the past 5 years, highlighting the design strategy, chemical synthesis, therapeutical applications, spectroscopic and pharmacological characterization, as well as the multifaceted roles of peptides. A comprehensive understanding of the tumor-targeted, "always-on" peptide-based NIR fluorescent probes will increase our knowledge of cancer diagnosis and benefit clinical cancer therapeutics.

The effect and mechanistic study of encequidar on reversing the resistance of SW620/AD300 cells to doxorubicin.

Encequidar, a gut-specific P-glycoprotein (P-gp) inhibitor, makes oral paclitaxel possible, and has been used in clinical treatment of metastatic breast cancer, however, its pharmacological effect and mechanism of reversal of drug resistance in drug-resistant colon cancer cells SW620/AD300 are still unknown. Herein, we first synthesized encequidar and demonstrated that it could inhibit the transport activity of P-gp, reduced doxorubicin (DOX) efflux, enhanced DOX cytotoxicity and promoted tumor-apoptosis in SW620/AD300 cells. Metabolomic analysis of cell samples was performedusing liquid chromatography Q-Exactive mass spectrometer, the results of metabolite enrichment analysis and pathway analysis showed that the combination of encequidar and DOX could: i) significantly affect the citric acid cycle (TCA cycle) and reduce the energy supply required for P-gp to exert its transport activity; ii) affect the metabolism of glutathione, which is the main component of the anti-oxidative stress system, and reduce the ability of cells to resist oxidative stress; iii) increase the intracellular reactive oxygen species (ROS) production and enhance ROS-induced cell damage and lipid peroxidation, which in turn restore the sensitivity of drug-resistant cells to DOX. In conclusion, these results provide sufficient data support for the therapeutical application of the P-gp inhibitor encequidar to reverse MDR, and are of great significance to further understand the therapeutic advantages of encequidar in anti-tumor therapy and guide clinical rational drug use.