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8/13/11

Dendrimers for cancer therapy

Dendrimers
Dendrimers were first discovered in the early 1980’s by Donald Tomalia and co-workers. Dendrimers are chemically synthesized nanoparticles in which a branching monomer is polymerized to give tree-like structures organized around a central molecule, resulting in an atomically defined, more or less spherical nanostructure. The structure of these materials has a great impact on their physical and chemical properties. As a result of their unique behavior dendrimers are suitable for a wide range of biomedical and industrial applications.
Applications
Dendrimer can easily be modified with molecules because of the presence of many functional chemical groups on the surface that provide added functionality to the dendrimer, such as molecules that target particular cells, and chemotherapy drugs as cargoes. Dendrimers can be used in molecular electronics for the storage of information or for nanoelectronics, as gene delivery agents or nanoscale reactors for catalysis, in addition to building blocks for nanotechnology. The novel dendrimers and other polymeric materials can also be used in a variety of separation and molecular recognition processes and as functional components of miniaturized "labs-on-a-chip."
Structure
According to Berkely Lab report, in a dendrimer, the branches are interlinked polymerized chains of molecules, each of which generates new chains, all of which converge to a single focal point or core. The surface of a dendrimer globe bristles with numerous chain-ends. During synthesis, these chain-ends can be designed to perform specific chemical functions. For example, they may be electrically charged so that the entire dendrimer functions as a polyelectrolyte. Other features, including the external size and internal architecture of a dendrimer can also be controlled during synthesis. This makes possible the creation of interior cavities or channels with properties different from those on the exterior and opens the door to dendrimers serving as vessels or hosts for guest molecules. In this capacity, dendrimers could serve as targeted drug.
Synthesis
The first synthesized dendrimers were polyamidoamines (PAMAMs). They are also known as starburst dendrimers. Dendrimers are generally prepared using either a divergent or convergent methods.
Divergent method
In the divergent methods, dendrimer grows outwards from a multifunctional core molecule. The core molecule reacts with monomer molecules containing one reactive and two dormant groups giving the first generation dendrimer. Then the new periphery of the molecule is activated for reactions with more monomers. This process is repeated for several generations and a dendrimer is built layer after layer. The divergent approach is successful for the production of large quantities of dendrimers.
Demerit
But problems occur from side reactions and incomplete reactions of the end groups that lead to structure defects. To prevent side reactions and to force reactions to completion large excess of reagents is required. It causes some difficulties in the purification of the final product.
Convergent method
In the convergent approach, the dendrimer is constructed stepwise, starting from the end groups and progressing inwards. When the growing branched polymeric arms, known as dendrons, are large enough, they are attached to a multifunctional core molecule. It is relatively easy to purify the desired product and the occurrence of defects in the final structure can be minimized. It becomes possible to introduce subtle engineering into the dendritic structure by precise placement of functional groups at the periphery of the macromolecule.
Demerit
Convergent growth method has several advantages. The convergent approach does not allow the growth of high generations because steric problems occur in the reactions of the dendrons and the core molecule.
Properties
In solution, linear chains exist as flexible coils; in contrast, dendrimers form a tightly packed ball. This has a great impact on their rheological properties. Dendrimer solutions have significantly lower viscosity than linear polymers. When the molecular mass of dendrimers increases, their intrinsic viscosity goes through a maximum at the fourth generation and then begins to decline. Such behavior is unlike that of linear polymers. For classical polymers the intrinsic viscosity increases continuously with molecular mass.
Anti-cancer drugs
Dendrimer can deliver cancer fighting drug to head and neck tumors. Head and neck cancer has been the more difficult malignancies to treat and after successful treatment patients suffer severely from the available therapies. Researchers at the University of Michigan have reported using a model study that dendrimers targeted to tumors and carrying anti-cancer drugs show great promise as potential therapy for head and neck cancer. Dendrimer decorated with folic acid on its surface delivers the drug methotrexate to head and neck tumors. The tumor-targeted nanoparticle delivers high doses of anticancer agents directly to head and neck tumors.



1 Responses to “Dendrimers for cancer therapy”

Leslie McIlroy said...
July 16, 2013 at 11:14 AM

I work for an immigration attorney who has a client with vast experience working with phosphorus dendrimers. His client would like to continue her research with phosphorus dendrimers in the United States, and we feel the United States could greatly benefit from her expertise. We are looking for an expert who would be willing to review our client’s publications and the like and, if appropriate, write a letter attesting to the importance of our client’s work and her extraordinary level of expertise in the field. Please contact me if this is something you would be interested in doing. Of course, reasonable compensation will be provided for your services. Please email me at 2013justthetwoofus@gmail.com if interested.


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