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  Theme-based Research Scheme–Call for Proposal

  Theme-based Research Scheme–Call for Preliminary Proposals

  Launch of New Joint Research Schemes

  Nanotherapeutics in Angiogenesis: Synthesis and in Vivo Assessment of Drug Efficacy and Biocompatibility in the Zebrafish Embryos

  Nimodipine suppresses chemokine release via inhibition of adenosine uptake in endothelial cells

  DNA-binding Activities of Some Alkaloids from Chinese Medicinal Herbs

  Development of a High Performance Liquid Chromatographic Method for the Quality Control of Rhizoma Smilacis Glabrae and its Derived Products

  Interactions between UGT isoenzymes and MRP transporters during the oral absorption process of Baicalein

  Gender Differences in the Regulation of Endothelium-Dependent Contracting Factor

  Areas of Excellence Scheme Project: Introducing the Work of the Hong Kong Institute of Economics and Business Strategy

  Areas of Excellence of Scheme Project: Building excellence in plant and agricultural biotechnology research

  RGC Collaborative Research Fund – Layman Summaries of Projects Funded in 2009/10 Exercise

Principle Investigator Dr. CHENG Shuk Han, Department of Biology and Chemistry, City University of Hong Kong

To grow and spread, tumors need blood vessels to provide nutrients. Scientists are trying to find ways to stop angiogenesis. Angiogenesis inhibitors stimulate cells to stop the angiogenes is process. Hence, angiogenesis inhibition therapy can help chemotherapy drugs and radiation therapy work more effectively when given in combination. Vascular integrins, in particular alpha-v-beta-3, are important regulators of angiogenesis, including tumor angiogenesis. The integrin alpha-v-beta-3 is highly expressed on activated endothelial cells and tumor cells but is not present in resting endothelial cells and most normal organ systems. The cyclic arginine-glycine-aspartic acid (RGD) peptide recognizes alpha-v-beta-3 integrin receptors and thus target to cancer cells. 

Dr. Cheng’s research team has shown that nanomaterials, such as carbon nanotubes, can be used as promising drug delivery vesicles. They have developed a new type of nanotherapeutics, namely multifunctional carbon nanotubes, to target and destroy aggressive ectopic angiogenesis. The generated nanoconjugates mainly accumulated in the blastoderm cells which facilities the drug delivery applications. To generate the anti-angiogenic agents, they have attached anti-angiogenic drug, together with targeting moieties and tracking dye, onto the same carbon nanotubes. The targeting molecules, RGD, can target newly formed blood vessels while the anti-angiogenic drugs Thalidomide can inhibit the angiogenesis process. The novel nanotherapeutic agents can prevent drugs from interacting with normal cells, thus avoiding side effects. 

The zebrafish system is an important model for studying human development and diseases. Transparency of zebrafish embryos facilitates visual inspection of cardiovascular system as well as of changes in blood vessel growth. Previous research has also shown that drugs causing anti-angiogenesis in human have similar effect in the developing zebrafish embryo. Dr. Cheng’s research team have successfully applied the zebrafish system to screen for angiogenic modulating activities in Chinese herbs and derived compounds. 

The biodistribution, efficacy and biocompatibility of the generated nanotherapeutics were tested in the transparent zebrafish embryos. The delivery vector carbon nanotubes showed good biocompatibility in the loaded developing zebrafish embryos, and no toxic effects were observed in the whole life cycle when they were loaded into the embryos just after fertilization. Carbon nanotubes conjugated with RGD illustrated efficient angiogenesis targeting and further mammalian cell xenograft assay demonstrated that the developed anti-angiogenic nanotherapeutics specifically inhibited the ectopic angiogenesis in zebrafish embryos.

The blood vessels of transgenic zebrafish embryos can be easily visualized under confocal microscope. While ectopic angiogenesis is a necessary for tumor growth and expansion, multifunctional nanotherapeutics was designed to target and destroy tumor angiogenesis specifically and simultaneously. 

This study attempts to capitalize on the highly reactive nature of the carbon nanotubes and conjugate several moieties onto the surface to achieve targeted delivery of small dosages of anti-angiogenic drugs to newly formed blood vessels. This study generated nanosized tools which can be used for specific and simultaneous delivery of treatment to tumor angiogenic sites. This project forms an essential part in our current drive to apply nanotechnology to improve human health. 

Dr Shuk-han CHENG
Department of Biology and Chemistry
City University of Hong Kong