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.

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 Materials1 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 plasmid2) 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.

Vitamin A in the Body

Vitamin A is absorbed into the body in the same way as dietary fat, and, as mentioned, absorption requires some fat. The vitamin enters the bloodstream and goes to the liver for either storage or immediate use. The liver stores 90 percent of the body's vitamin A, and this supply can sustain most people for six months to a year. When cells need vitamin A, the liver makes a carrier called retinolbinding protein (RBP) to transport the vitamin in blood, since vitamin A is fat soluble. And it's a good thing that vitamin A gets around because the jobs it has to do are many and varied: from your toes to your eyes, this nutrient is a must.

One of vitamin A's most important and well-known roles is in maintaining vision. It achieves this through a compound called rhodopsin, also known as visual purple, which enables the eye to adapt to changes in light. When the retina receives light, it splits the rhodopsin molecule into its two constituents, opsin and retinal, or active vitamin A. In the dark, they recombine to form rhodopsin. Every time this reaction occurs, you use up some retinol. This is the reason why one of the first signs of deficiency is night blindness.

Another vital function is in the formation and maintenance of epithelial tissue. These tissues form the body's first line of defense against infections and carcinogens (cancer-causing agents) by serving as barriers to invaders. Epithelial tissues include the skin and membranes lining the eye and mouth cavities, stomach and intestines, lungs, and other organs. Some animal studies show that both retinoids and carotenoids can prevent cancers originating in epithelial tissue.

Vitamin A also plays a critical role in growth and reproduction. Even the earliest studies showed the vitamin's importance by causing growth failure in deficient rats, but scientists have yet to discover how it works. Most think that vitamin A is essential in the growth of soft tissues and bone by affecting protein synthesis, cell division, or cell membrane stability. Female animals who are vitamin A-deficient abort or produce malformed offspring. However it works, normal reproductive function in both sexes depends on adequate vitamin A. Results from human studies show that vitamin A deficiency causes degeneration of the sex glands and eventual sterility—now there's a scary thought!

Source:

The Vitamin Sourcebook

Vitamin A Introduction

Although vitamin A, and especially its cousin beta-carotene, is currently a nutrient of popular interest, it's had a long history. Vitamin A was the first of the fat soluble vitamins to be discovered. In 1913, two groups of American researchers unveiled the mystery simultaneously. Both research teams found that animals became sick when fed fat-free diets. The animals failed to grow and suffered a high rate of infection and eye problems, which were relieved by feeding cod liver oil or butterfat.

Ten years later, a Danish researcher reported that a condition in children, xerophthalmia, which can lead to permanent blindness, could be  prevented by adding butterfat or oil to their diets. And long before that, history records that the ancient Egyptians were the first to cure night blindness by applying juice squeezed from liver into the eyes of those afflicted. The Greeks subsequently advocated eating liver, in addition to its topical application, for the cure.

The related compound, beta-carotene, arrived on the scene in 1932 when researchers discovered that vegetable foods also possessed vitamin A activity. Closer analysis of vegetables uncovered the class of compounds known as carotenoids, which includes carotene and other yellow pigments.

These pigments give the brilliant colors to red and yellow vegetables. Dark green vegetables also contain carotenoids, but the color is masked by the chlorophyl pigment. The same principle keeps leaves from changing color until fall. 

Names for vitamin A can be confusing unless you look at the chemical formula. The chemical formula for biologically active vitamin A is an alcohol since it contains a hydroxyl group (oxygen and hydrogen). The name retinol is derived from this alcohol component and vitamin A's function in the retina of the eye. Vitamin A is a generic term for all compounds that have the biological activity of retinol, excluding the carotenoids.

The biological activity of a nutrient tells you about its ability to carry out important functions in the body. Other names and forms include retinyl esters, retinal, retinaldehyde, and retinoic acid. Retinoic acid can carry out some, but not all, of the functions of retinol. The term retinoid refers to all forms of retinol both in natural and synthetic forms.

Carotene compounds are called provitamins since they serve as precursors to vitamin A. Humans and animals can't synthesize carotene, but both can convert it to vitamin A in the liver. Of all the carotenoids, beta-carotene gives you the highest amount of active vitamin A, which is why scientists consider it the most important of the carotenoids. In addition, in the average American's diet, beta-carotene supplies almost two-thirds of the vitamin A requirement. More recently, scientists are finding that other carotenoids, like lycopene in tomatoes, offer other health advantages.