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Nanoparticles successfully deliver RNA interference in cancer patients
Chemistry World ^ | 21 March 2010 | Simon Hadlington

Posted on 03/22/2010 7:07:54 PM PDT by neverdem

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. 

Nanoparticle

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

M E Davis et al, Nature, 2010, DOI: 10.1038/nature08956

Also of interest

Nanoparticles in action

Combination nanoparticles to fight cancer

13 May 2009

Multitalented nanoparticle can track down, illuminate and treat cancer cells


Modifying siRNA

Stabilising RNAs enhances gene silencing in tumours

25 January 2010

Chemically modified, stabilised RNA molecules find their way into cells more easily, claim researchers



TOPICS: Culture/Society; News/Current Events; Technical
KEYWORDS: nanoparticles; rnai; rnainterference; sirna
Cancer genes silenced in humans

Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles

1 posted on 03/22/2010 7:07:55 PM PDT by neverdem
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To: neverdem

That’s encouraging news! Maybe it can be tested on cancer we all face known as Congress.


2 posted on 03/22/2010 7:10:38 PM PDT by Man50D (Fair Tax, you earn it, you keep it! www.FairTaxNation.com)
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To: neverdem

3 posted on 03/22/2010 7:16:05 PM PDT by garjog (Used to be liberals were just people to disagree with. Now they are a threat to our existence.)
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To: garjog

Could we inject this substance into Barack H Obamas rectum and see if it will cure the Shaft he just gave us all?


4 posted on 03/22/2010 7:18:53 PM PDT by Michigan Bowhunter
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To: garjog

Could we inject this substance into Barack H Obamas rectum and see if it will cure the Shaft he just gave us all?


5 posted on 03/22/2010 7:19:13 PM PDT by Michigan Bowhunter
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To: girlangler

ping for later


6 posted on 03/22/2010 7:19:28 PM PDT by girlangler (Fish Fear Me)
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To: El Gato; Ernest_at_the_Beach; Robert A. Cook, PE; lepton; LadyDoc; jb6; tiamat; PGalt; Dianna; ...
Walnuts slow prostate tumors in mice

Study explores link between sunlight, multiple sclerosis

Virtual colonoscopy allows detection of unsuspected cancers beyond colon

Poorly understood cell plays role in immunity against the flu

FReepmail me if you want on or off my health and science ping list.

7 posted on 03/22/2010 7:32:20 PM PDT by neverdem (Xin loi minh oi)
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To: neverdem

I’m sorry, sir, but this treatment is not cost effective. DENIED!!


8 posted on 03/22/2010 7:48:14 PM PDT by beethovenfan (If Islam is the solution, the "problem" must be freedom.)
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To: beethovenfan

Yes, and would tend to keep too many people living.


9 posted on 03/22/2010 7:49:08 PM PDT by John W
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To: neverdem

Sounds like they are moving closer and closer to a REAL cure here.


10 posted on 03/22/2010 7:51:25 PM PDT by Salvation ("With God all things are possible." Matthew 19:26)
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To: garjog

I didn’t know Barack had eight legs?


11 posted on 03/22/2010 8:35:48 PM PDT by diamond6 (Expose Planned Parenthood: http://www.youtube.com/watch?v=cYaTywSDmls)
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To: diamond6

You probably thought he was a bug and had only 6. That’s understandable.


12 posted on 03/22/2010 8:44:06 PM PDT by ProtectOurFreedom
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To: Salvation

I’m sure the research will be shut down any day now.


13 posted on 03/22/2010 8:44:38 PM PDT by ProtectOurFreedom
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To: neverdem

The side note here is that Humans are discovering things that change life’s situations ...

I’d call such things evolution oriented.


14 posted on 03/22/2010 9:04:22 PM PDT by OldNavyVet (One trillion days, at 365 days per year, is 2,739,726,027 years. That's 2.739 billion years.)
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To: ProtectOurFreedom

LOL!!!!


15 posted on 03/22/2010 9:21:13 PM PDT by diamond6 (Expose Planned Parenthood: http://www.youtube.com/watch?v=cYaTywSDmls)
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To: Man50D

Well Hell, I been saying that all along.


16 posted on 03/22/2010 9:25:12 PM PDT by ully2 (ully)
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