Nanocarriers that can kill tumors with drugs and DNA

A breakthrough technology developed at IBN can potentially lead to more effective treatment methods for cancers

SINGAPORE, September 27, 2006 – A team of scientists in Singapore has developed nanoparticles that can carry both small molecular anticancer drugs and nucleic acids simultaneously for improved cancer therapy. This groundbreaking work was published online in Nature Materials (1) on September 24, 2006, a leading materials science journal.

The uniqueness of the new technology from the Institute of Bioengineering and Nanotechnology (IBN) lies in the design of a special biodegradable carrier (cationic core-shell nanoparticle), which can enclose drug molecules and allow therapeutic nucleic acids to bind onto it.

It can efficiently introduce DNA into a cell to be incorporated into its genetic make-up, i.e. induce high gene expression level, especially in both human and mouse breast cancer cell lines, and mouse breast cancer model. The co-delivery of small molecular drugs with nucleic acids can improve gene transfection efficiency, reduce side-effects of these drugs, and achieve the synergistic effect of drug and gene therapy for the more effective treatment of cancer.

Results have shown that the co-delivery of an anti-cancer drug (paclitaxel) with a highly potent anti-tumor ‘messenger molecule’ (IL-12 encoded plasmid (2) ) using the carrier suppressed cancer growth more efficiently than the delivery of either paclitaxel or the plasmid in mice bearing 4T1 breast cancer.

In collaboration with Nanyang Technological University, experiments were also conducted to co-deliver paclitaxel and small interfering RNA (siRNA) targeting a protein that prevents cell death (Bcl-2) to MDA-MB-231 human breast cancer cell line. The cancer cells became more susceptible to the effects of the drug, due to the additional effect of the siRNA targeting Bcl-23.

This special carrier can also be potentially used to co-deliver therapeutic nucleic acids to prevent cancer cells from developing resistance to multiple drugs4. This, coupled with the simultaneous delivery of specific anticancer drugs, could enhance the therapeutic effects of such drugs.

Other scientists in this field have tried to use liposomes made from cationic (charged) lipids to transport drugs and DNA. The carrier developed at IBN is self-assembled from a biodegradable cationic copolymer. Hence, it is more easily produced and its size and characteristics are more easily controlled compared to liposomes. More importantly, it can deliver nucleic acids more effectively.

“These nanocarriers developed by our team have a variety of applications in medication and as a gene transfection agent for biological research,” said Dr Yi-Yan Yang, who led the project team comprising Yong Wang, Shujun Gao, Wen-Hui Ye and Ho Sup Yoon. “They provide an interesting approach to improving the efficiency of cancer treatments.”

United States and PCT (Patent Cooperation Treaty) patents have been filed by IBN on the invention.

(1) Y. Wang, S. Gao, W.-H. Ye, H. S. Yoon and Y. Y. Yang, “Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer,” Nature Materials, published online on September 24, 2006.
Note: This paper was subsequently published in the October 2006 Vol 5 issue (pp 791-796) of Nature Materials.

(2) IL-12 is a highly potent anti-tumor cytokine, and may also overcome paclitaxel-mediated T cell suppression.
A member of A*STAR’s Biomedical Sciences Institutes (Co. Reg. No. 199702109N)

(3) The suppression of the anti-apoptotic activity of Bcl-2 by the siRNA made the cells more sensitive to paclitaxel, leading to greater cytotoxicity of paclitaxel.

(4) The therapeutic nucleic acid may be a vector encoding an antisense molecule directed against the P-glycoprotein mRNA in the target cell. Such a system can inhibit P-glycoprotein expression by the target, and hence, incapacitate its ability to establish multi-drug resistance, a common trait among cancer cells. This, together with the cytotoxic effects of the anti-cancer drug, should enhance the therapeutic effect of the system.

About the Institute of Bioengineering and Nanotechnology (IBN)
The Institute of Bioengineering and Nanotechnology (IBN) is a member of the Agency for Science, Technology and Research (A*STAR). Established in March 2003, the Institute’s mission is to establish a broad knowledge base and conduct innovative research at the interface of bioengineering and nanotechnology. Positioned at the frontiers of engineering, IBN is focused on creating knowledge and cultivating talent to develop technology platforms that will spur the growth of new industries. IBN also fosters an exciting, multidisciplinary research environment for the training of students and young researchers to spearhead biomedical advancement in Singapore.

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Published: 24 Jan 2007

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Medicine