Two Kinds Of Near-infrared Fluorescent Dyes Used In Targeted Drug Delivery System

With mortality rate from cancer increasing over years, cancer treatment is attracting more and more attention. Chemotherapy, an important way to treat cancer, should never be under-estimated. As traditional cancer chemotherapy is often accompanied by significant systemic toxicity to the patients, more and more drug research transfers to tumor-targeting drug delivery system. However, antitumor drugs in targeting drug delivery system generally have little if any fluorescence making it impossible to visualize the transfer process. Herein, we tried to prepare targeting fluorescent probes using the near-infrared dyes, which would make visualizing the transfer process possible and thus lay the foundation for subsequent targeting drug design.The paper was focused on the design of two near-infrared fluorescent probes taking advantage of the high expression of nitroreductase under hypoxic tumor environment and the high expression of cathepsin B in tumor. In the first part, we designed the near-infrared fluorescent probe in connection with nitroreductase in tumor and synthesized a common linker. A possible five/six-membered ring closed-loop mechanism was proposed. In order to verify this mechanism, the corresponding derivatives and appropriate chemical reduction were carried out. The results showed that some compounds cannot be self-closed loop, surmising that it may be caused by steric hindrance and fracture-related bonds. The results did not consistent with the original design of the common linker, so we did not go on further study. In the second part, a branched linker that is designed and synthesized in our laboratory, and the near-infrared dye with "off- on" nature containing hydroxyl group were designed to synthesize the near-infrared fluorescent probe in connection with cathepsin B in tumor. Then its fluorescent properties and the possible mechanism of coloration with the cathepsin B were proposed. To verify its mechanism, in vitro experiment was carried out. The results showed that it could release the near-infrared dye in the role of cathepsin B to achieve the purpose of coloration.The near-infrared (NIR) fluorescent probe taking advantage of the high expression of cathepsin B in tumor can achieve the purpose of process visualization. The results illustrate that the near-infrared fluorescent probe has instructive aspect in the design of tumor-targeted drug delivery system and can assist in designing better targeted drugs, providing a basis for the future application of targeted drug delivery systems.