This is not just about a new method of drug delivery, rather it is about a new class of treatments that may be possible because of this new drug delivery technique.

This work was carried on by a rather large research group from  several Canadian and US institutions [1] :

Here they are : Avi Schroeder, Michael S. Goldberg†, Christian Kastrup†‡§, Yingxia Wang‡, Shan Jiang†‡, Brian J. Joseph‡, Christopher G. Levins†‡, Sneha T. Kannan†, Robert Langer†‡, and Daniel G. Anderson*et.  al.

The group  developed nanoparticles that can be controllably triggered to synthesize proteins. Nanoparticles  are ultra small, on the order of micrometers. Keep in mind that 1 micrometer is about 5 millionth of an inch…  The size of the nanoparticle size allow one on one interaction of the drug molecule and the diseased cell. A little bit like aiming a bullet to a target  or a bucket of water to a flame source. As opposed to the shotgun approach or helicopter dousing a bucket.

 

Lipid Nanoparticle and it’s Protein Synthesis Cargo

 

There is a Wikipedia entry on targeted drug delivery [2]. and their illustration is similar to the figure above, but the nanoparticle cargo is  less complex and does not seem to be awaiting photoactivation.  Note that the drug container is a liposome vesicle or a  small bubble enclosed by lipid bilayer. Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols. However, the Wikipedia sketch is  dated 1999, so the idea is not new. It is just that the method is so complex that it takes all this time to develop.

 

 

A similar delivery method was illustrated by  in an MIT release [2] about drug delivery, also by by a nanosize liposome. The goal was also targeted cancer chemotherapy delivery. The team lead by Omid Farokhzad at Brigham and Women’s Hospital and MIT Institute Professor Robert Langer.

 

A nanoparticle filled with a chemotherapy drug targets a cancerous cell (MIT) Image / Nicolle Rager Fuller, Sayo-Art

 

Study [1] used a phospholipid vesicles formed around a bacterium extract, E. coli S30,  as well as other protein.

This can be illustrated by a Wikipedia photo of a Bacillus subtilis as an example of a natural Liposome vesicle (from the Weizman Institute, Israel)

 

Bacillus subtilis as an example of a natural Liposome vesicle (Allon Weiner, The Weizmann Institute of Science, Rehovot, Israel)

So far, we just talked about the drug carrier or vector. 

The  Canadio-American work’s novelty is that  the cargo are the building material for the synthesis of a protein.One of the possibility of this new technology would be to generate therapeutic proteins that provoke a reaction of the immune system against cancer or other ills ( Immunogenicity).  Immunogenic proteins are the most promising cargo because they initiate a rection by the immune system of the host.

The full technique technique is quite complex: These particles served as nanofactories capable of producing protein. The protein synthesis is initiated by” irradiating micrometer-scale regions on the time scale of milliseconds”, in other words pin operation both in space and time.

As far as we are concerned, this should have a bright  future. But where does the FDA stand on this?

Seems that the system is a bit overwhelmed, quoting [5]:

“…By tailoring the chemistry and identity of variable nanoparticle constituents, it is possible to achieve targeted delivery, reduce side effects, and prepare formulations of unstable (e.g., siRNA) and/or highly toxic drugs … With these benefits arise new challenges in all aspects of regulated drug development and testing…”

Nethertheless, the FDA approved in 2005 Nanoparticle Paclitaxel (Abraxane) for the treatment of metastatic breast cancer.  There are lots of caveats, but, once a cancer is metastastic, or generalized to the whole body, some caution are obviously waved…

Sources

  1. American Chemical Society ; Nano Letters ; “Remotely Activated Protein-Producing Nanoparticles” ; March 2012
  2. MIT News ;Drug Delivery by a nanoparticle ; 2008
  3. Clinical Therapeutics ; “Immunogenicity of therapeutic proteins: clinical implications and future prospects.” ; 2002
  4. Wikipedia/Immunogenicity ; 1999
  5. Methods of molecular biology ; “Nanoparticle therapeutics: FDA approval, clinical trials, regulatory pathways, and case study” ; 2011
  6. National Cancer Institute ; “ FDA Approval for Nanoparticle Paclitaxel” ; Jan 2005
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