DING Ya and HUANG Zhangjian Collaborate to Report on the Synergistic Effect of Nano-coordination Polymers on Nitric Oxide and Chemical Kinetics

Release date:2019-04-18  Release:主页英文版

Recently, Nano Letters (Impact Factor 12.08), an authoritative journal in the field of materials science, published the latest research results of the collaboration between Professor DING Ya and Researcher HUANG Zhangjian of China Pharmaceutical University——Nanoscale coordination polymers for synergistic NO and chemodynamic therapy of liver cancer. Postdoctoral fellow HU Yihui and Ph.D. student LU Tian are the co-first authors of this article. Professor DING Ya and Researcher HUANG Zhangjian are the correspondent authors of this article.

High concentrations of nitric oxide (NO) have been shown to inhibit tumor growth. Therefore, improving the targeting and effectiveness of NO in intratumoral release and treatment is the key to achieving NO anti-tumor therapy. The researchers designed and synthesized a NO donor with a double carboxyl group, and chelated with ferrous ions by simple mixing, co-precipitation, and ion exchange to form a nanometer-sized coordination polymer. The coordination polymer contains only NO and ferrous ions, and can be regarded as a zero carrier nano drug, which remains stable in the systemic circulation and accumulates in the tumor site through enhanced tumor penetration and retention effects. The NO donor in the polymer structure rapidly releases NO under the condition of high concentration of glutathione in the tumor cells, and ferrous ions produce hydroxyl radicals and peroxy radicals respectively by Fenton reaction and Haber-Weiss reaction under high oxygen concentration H2O2 micro-environment. Hydroxyl radicals exert pharmacokinetic treatment (CDT) efficacy. The peroxy radical reacts rapidly with the released NO to form a more oxidizing peroxynitrite, which enhances the therapeutic activity of NO. Hydroxyl radicals and peroxynitrites exert synergistic therapeutic effects on chemical kinetics and NO. The synergistic mechanism is clearly clarified by the detection of various free radicals described above. Compared with normal hepatocytes, the polymer has the ability of liver tumor cells to target free radical release; in the mouse liver xenograft model, CDT and NO exhibit synergistically enhanced antitumor activity and are less toxic to normal tissues/cells.

This strategy of using a pro-drug molecule as a framework material to directly construct a nanomedicine solves the key scientific problems of drug leakage in advance, insufficient drug release, and low carrier atomic economy. The obtained coordination polymer structure is clearly controllable, the drug loading is high, the systemic circulation is stable, the tumor treatment has high selectivity and specificity, the therapeutic effect is excellent, and the toxic and side effects are small. This work not only provides a new strategy for the synergistic treatment of tumors for basic research, but also improves the pharmacodynamic properties and drug-forming properties of NO donor drugs in anti-tumor. At present, it has applied for Chinese patents and international patents, and has good application and transformation prospects.