Reading Reaction Journal#1

Nanoparticles successfully deliver RNA interference in cancer patients

US scientists have created a nanoparticle drug that acts like a stealth bomber to smuggle its RNA-interfering payload past the body's defence systems and drop it on to cancer cells. It is, say the researchers, the first example of a nanoparticle that can seek out its target after being injected into the bloodstream and paves the way for the selective targeting of cells and tissues in the body while causing only little 'collateral damage' in the form of side effects.

"This is the first proof of concept that RNA interference can occur in a human from delivered siRNA"
- Mark Davis, California Institute of Technology

The system aims to exploit the phenomenon of RNA interference (RNAi), where short sequences of double-stranded RNA, called small interfering RNA or siRNA, can trigger the disruption of the manufacture of certain proteins in a cell. RNAi holds great promise for the treatment of many diseases such as cancer, but a number of hurdles remain, not least delivering the RNA to the target cell.

'If you use pure RNA it is very quickly degraded in the bloodstream,' says Mark Davis, of the California Institute of Technology, whose team carried out the new research. Even if the RNA is stabilised to survive in the blood, it can then be excreted via the kidneys. If this can be avoided, the RNA must then be taken to its specific target tissue.

Davis's team has spent 15 years on the problem and has come up with a multi-component system that tackles each of the challenges. A cyclodextrin-based polymer (CDP) self-assembles with siRNA to create the basic nanoparticle in which the siRNA is protected from degradation. Polyethylene glycol containing the cycloalkane adamantane (AD-PEG) decorates the surface of the particle to provide stability against aggregation and binding to unwanted entities in the blood. Finally a targeting ligand is attached to the surface, the protein transferrin (Tf), which homes in on excessive transferrin receptors present on the surface of the cancer cells being targeted.

The various components self-assemble into a targeted nanoparticle when mixed together © Nature

When the particles were injected into patients with a form of cancer called melanoma, the researchers found that the particles accumulated in the cancer cells, and that the greater the dose of nanoparticles, the greater the accumulation. Furthermore there was evidence that RNAi was occurring in the cancer cells.

'This is the first example of dose-dependent localisation of nanoparticles within cancer cells from systemic injection,' says Davis, 'and the first proof of concept that RNA interference can occur in a human from delivered siRNA.'

Snow Stolnik-Trenkic, an expert in drug delivery systems at the University of Nottingham in the UK, says, 'At present effective siRNA delivery is considered the bottleneck in the proof of the concept of siRNA therapeutic potential and the translation of this potential into the clinic. The big advance of this new work is that it has for the first time been done in humans.'

References

Davis M. E. et al. (2010). Nanoparticles successfully deliver RNA interference in cancer patients Nature DOI: 10.1038/nature08956.

http://www.rsc.org/chemistryworld/News/2010/March/21031001.asp

Vocabulary

Nanoparticle: really small particle

Stealth: movement that is quiet and careful in order to avoid notice, or secret or indirect action

Smuggle: to take things or people to or from a place secretly and often illegally

Pave: to cover (an area of ground or a road) with materials such as stone, concrete, or bricks that will form a hard, level surface

Sequences: a series of related things or events, or the order in which things or events follow each other

Hurdles: a frame for jumping over in a race

Manufacture: a special place

Tackle: to attack or to deal with (something)

Ligand: a kind of chemical elements

Therapeutic: having a healing effect; tending to make a person healthier

Exploit: to use (something) for your own benefit

Summary

This article talks about how humans can use nanoparticles to bypass some important systems and to kill cancer directly. According to the article, author talks about how using RNAi can cure a lot of diseases like cancer. However, it still has lots of impediments; at least it doesn’t deliver the RNA to the target cell. Davis's teams have come out with each of the challenges’ answers, and try to take a test for a cancer victim. Snow Stolnik-Trenkic is an expert in drug delivery systems at the University of Nottingham in the UK. Now he says: “The big advance of this new work is that it has for the first time been done in humans.”

Reaction

My major is biology, so I’m crazy about reading some articles about human’s genes or what’s the function of Molecular Genetics like RNA and DNA. This article gives me some new information and new technologies.

I had already known that RNA could save some genetic information if the cell dose not has a cell nucleus. The cell doesn’t have a cell nucleus, which means it doesn’t have DNA. However, I never knew RNA could cure cancer, which is the most terrible disease that a person can get in the world. I have some questions about this article. The first one is that according to the article, the author says “Even if the RNA is stabilised to survive in the blood, it can then be excreted via the kidneys. If this can be avoided, the RNA must then be taken to its specific target tissue.” In my opinion, that RNA wants to stabilize to survive in the blood is possible, but that if wants to go via the kidney, that is impossible. Why do they still to make such ridiculous assumptions? They can choose to let the RNA be stablilsed in blood cells; after that, to make blood cells blast. May be it is easy to get to its destinations. The second question, in the article it says “the RNAi occur in the cancer cells.” I just want to ask, if the cancer cell’s gene is mutating, but RNA’s gene is not mutating, what will happen next? Will Cancer outbreak? Or Cancer change genes?

This article lets me learn about new information about RNA and nanoparticles. They get together to struggle with diseases, and I also know new technologies which are called RNAi and siRNA. These technical terms are not easy to use because if you have a little bit mistakes, it will make them unable to convert to protein which is what you want.