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"Development of novel metal-based cancer therapy"

Our research is primarily focused on the design and development of innovative metal-based chemical systems and their subsequent application in biological systems with a long-term goal of improving cancer therapy. Currently, cancer is the second leading cause of death in the United States, only behind cardiovascular disease, and it is projected to become the leading cause of death within 16 years according to American Society of Clinical Oncology. In 2013, approximately 0.6 million U.S. citizens died from cancer, and over 1.6 million U.S. citizens became new cancer patients. The number of new cases is expected to increase nearly 45% by 2030. So far, most types of cancer are still incurable, and development of effective cancer treatments remains at a slow pace. Since 1975, the survival rate for cancer patients has only increased by 3.4%. Several major issues account for the slow development of cancer therapy, including the limited efficacy of current therapeutics and the shortage of efficient drug delivery systems. Research in the Zheng lab will focus on developing chemical tools that can benefit cancer research with respect to these limitations. The tools we are working on are based on metal complexes.

Metal complexes play an important role in cancer therapy. Cisplatin, a platinum complex, was demonstrated to be effective in treating cancer in 1969. By virtue of cisplatin, testicular cancer became one of the few types of cancer that are curable, with the survival rate of patients with testicular cancer being greater than 90%. Cisplatin and its analogous, carboplatin and oxaliplatin, are currently FDA-approved anticancer drugs that are widely used in chemotherapy for cancer patients with testicular, ovarian, head and neck, lung, and colon cancer. Ñý¼§Ö±²¥ 50% of cancer patients with chemotherapy are treated with these platinum drugs. The development of new metal-based drugs is, however, very slow, with most of the research focusing on compounds that are similar to the FDA approved platinum species. Such a drug design strategy favors development of drugs with common intrinsic cytotoxicity and mechanisms to drugs currently in the clinics. Deviating from the traditional approach, we seek to develop novel tools for cancer research based on innovative rationally designed metal-based chemical systems with an emphasis on new applications that target important questions. Our work will focus on applying innovative metal-based chemical systems in combination with nanotechnology and cancer biology to provide new tools to address important issues in cancer research with a long-term goal of improving cancer therapy.

Selected Publications

1. Zheng, Y.-R.; Suntharalingam, K.; Johnstone, T. C.; Lippard, S. J. Encapsulation of Pt(IV) Prodrugs within a Pt(II) Cage for Drug Delivery. Chem. Sci. 2015, 6, 1189.
2. Miller, M. A.; Zheng, Y.-R.; Gadde, S.; Pfirschke, C.; Zope, H.; Engblom, C.; Kohler, R. H.; Iwamoto Y.; Yang, K. S.; Askevold, B.; Pittet, M.; Lippard, S. J.; Farokhzad, O. C.; Weissleder, R. Tumor associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug. Nat. Commun. 2015, 6, 8692.
3. Zheng, Y.-R.; Suntharalingam, K.; Johnstone, T. C.; Yoo, H.; Lin, W.; Brooks, J. G.; Lippard, S. J. Pt (IV) Prodrugs Designed to Bind Non-Covalently to Human Serum Albumin for Drug Delivery. J. Am. Chem. Soc. 2014, 136, 8790.
4. Zheng, Y.-R.; Lan, W.-J.; Wang, M.; Cook, T. R. Stang, P. J. Designed Post-Self-Assembly Structural and Functional Modifications of a Truncated Tetrahedron. J. Am. Chem. Soc. 2011, 133, 17045.
5. Zheng, Y.-R.; Zhao, Z; Wang, M.; Ghosh, K.; Pollock, J. B.; Cook, T. R.; Stang, P. J. A Facile Approach toward Multicomponent Supramolecular Structures: Selective Self-Assembly via Charge Separation. J. Am. Chem. Soc. 2010, 132, 16873.
6. Zheng, Y.-R.; Stang, P. J. Direct and Quantitative Characterization of Dynamic Ligand Exchange between Coordination-Driven Self-Assembled Supramolecular Polygons. J. Am. Chem. Soc. 2009, 131, 3487.