Ding Ya and Huang Zhangjian’s findings in materials science published by Nano Letters

Release date:2019-04-09  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 Professor Ding Ya and Professor Huang Zhangjian, China Pharmaceutical University, Nanoscale coordination polymers for synergistic NO and chemodynamic therapy of liver cancer.  Dr. Hu Yihui and Ph.D. student Lu Tian are the co-first authors. Professor Ding Ya and researcher Huang Zhangjian are correspondent authors.

High concentrations of nitric oxide (NO) have been confirmed to inhibit tumor growth. Therefore, improving the targeting and effectiveness of NO release in tumor and treatment is the key to achieve 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 nanometre-sized coordination polymer. This coordination polymer, which only contains NO and ferrous ions and can be regarded as a zero carrier nano drug,  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. Ferrous ions produce hydroxyl radicals and peroxy radicals respectively by Fenton reaction and Haber-Weiss reaction under high tumor concentration of H2O2 micro-environment. Hydroxyl radicals play the role of chemical kinetic therapy (CDT); peroxygen radicals react rapidly with the released NO to form more oxidizing peroxynitrite anions, which enhances the therapeutic activity of NO. Hydroxyl radicals and peroxynitrite anions exert synergistic therapeutic effects on chemical kinetics and NO. Through the detection of the above various free radicals, the synergistic mechanism is clearly clarified. Compared with normal hepatocytes, the polymer has the ability to target free radical release from liver tumor cells. In the mouse liver xenograft model, it exhibits synergistic enhanced anti-tumor activity of CDT and NO, and is less toxic to normal tissues/cells.

This strategy of using a pro-drug molecule as a framework material to directly construct nano-drugs solves the key scientific problems of drug leakage in advance, insufficient drug release, and low economy of carrier atomic. 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 synergistic treatment of tumors for basic research, but also improves the pharmacodynamic properties and drug-forming properties of NO donor drugs in anti-tumor. Now it has applied for Chinese patents and international patents with good applications and transformation prospects.