Since established in 2007, Nankai University’s College of Pharmacy, in line with the university’s commitment to boost its capacity to serve public good, has been committed to easing patient symptoms. Integrating Nankai’s strengths in chemistry, biology, medicine, pharmaceutical science, economics and more, it educates young talented students for careers in the pharmaceutical industry and develops effective drugs for improving health.
Aligned to national priorities, a series of technology platforms have been established via domestic and international partnerships, undertaking research from lead discovery to pre-clinical development. Focusing on developing novel drug candidates and key technologies, researchers target major public health concerns, including cancer, infectious diseases, metabolic diseases, organ fibrosis, diabetes, and cerebrovascular diseases.
Breaking the silence of tumour suppressor genes
Researchers from the College of Pharmacy have developed nucleic acid-based lead compounds that could potentially treat a variety of cancers.
Tumour suppressors can protect against cancer formation, but small fragments of RNA, called microRNAs, in cancer cells, can be used to reduce the expression of these suppressor genes, making them ‘silent’. As some microRNAs target multiple genes, several tumour suppressor genes are downregulated together by a single microRNA.
Low expression of three tumour suppressor genes — KLF17, CDH1 and LASS2 — has been identified in many tumours, and their silence correlates with poor survival rates. A specific RNA fragment called microRNA-9 was found to be the one to downregulate the expression of these three genes simultaneously. Removing microRNA-9 in cancer cells may increase the expression of the tumour suppressor genes, and restore their protective function.
A team at the College of Pharmacy has designed small circular single-stranded DNAs (CSSDs), which contain the binding sites of microRNAs, and can act as ‘sponges’ to absorb microRNAs and reduce the level of free microRNAs.
CSSD-9, one of these artificial CSSDs, contains four successive binding sites of microRNA-9. It is stable and resistant to degradation in vivo. The team found that CSSD-9 can effectively inhibit cancer progression and metastasis by adsorbing microRNA-9 and increase the expression of tumour suppressor genes KLF17, CDH1 and LASS2 in cancer cells. They also used nano-particles as a vehicle to improve the delivery efficiency of CSSD-9. Its anti-cancer efficacy was more potent for tumour cells with high levels of microRNA-9, such as liver cancer, breast cancer, lung cancer, ovarian cancer and cervical cancer. Experiments both in vivo and in vitro found that CSSD-9 had little toxicity to normal cells and normal tissues of mice, and, to a certain extent, enhanced immune function in vivo.
“This novel anti-cancer strategy of designing CSSDs to absorb a specific microRNA and increase expression of tumour suppressor genes may become a significant therapeutic tool,” said the project leader, Yang Cheng, a professor in Nankai’s College of Pharmacy. “It has advantages over traditional anti-cancer treatment that mainly targets an oncogene.”
Collaborating with the pharmaceutical industry
Keen to address urgent demand for new drugs, researchers at the College of Pharmacy are joining with industry to translate their research results into pharmaceutical products. One example is the recent collaboration established with the China Pharmaceutical Research and Development Center company, part of China Resources Pharmaceutical Group, to develop a new drug for treating a colonic disorder.
Epidemiological data show that more than 70 million people in China suffer from slow transit constipation, a common colonic functional disorder, and its incidence is increasing year by year. This disease seriously affects quality of life, and may cause many other complications. The team at Nankai’s College of Pharmacy designed and developed a prokinetic agent CP0119, which can stimulate peristalsis — the symmetric contraction and relaxation of gut muscles.
CP0119 promotes the contractile function of intestinal myocytes by inducing the aggregation of actin, a protein that forms the contractile filaments of muscle cells. The safety evaluation, pharmacokinetics, pharmacodynamics and pharmacology of CP0119 have been studied, showing that CP0119 meets the criteria of pharmaceutical properties such as pharmacodynamic effects, safety and stability, tissue selectivity, synthetic and technologies to scale production. It overcomes many of the flaws associated with existing drugs, such as side-effects, resistance and poor patient compliance, with bright market potential.
This project is of great significance for the treatment of colonic diseases, and the Nankai research team is working hard to bring forward development, hoping to help patients sooner.
Through collaborations with the State Key Laboratory of Medicinal Chemical Biology (SKLMCB) and Tianjin International Joint Academy of Biomedicine, the College of Pharmacy has also established an innovative drug R&D platform to promote translational application of research results from academic labs.
“It’s our remit to support the Chinese biomedical industry with our knowledge and efforts,” said Yang, who is also the dean of the college. A strong faculty team and a comprehensive R&D system have been established to perform basic studies and develop key technologies in support of green, safe and efficient drug discovery.
“Talent education is another aspect and an important responsibility of the college,” said Yang. “We need to foster students, equipping them with strong biomedical and multidisciplinary knowledge covering the entire line of the pharmaceutical industry.”
With rich educational resources and dedicated efforts from faculty members, graduates from the college are well received by employers, with many becoming key influencers that take on great responsibilities and make a real difference in their institutions and workplaces.