Queue the new findings of the Chilkoti lab at Duke University who have demonstrated that adding a poly(ethylynglycol) (PEG) chain by polymerisation to the protein drug can increase the retention of said protein in the blood. It does this by effectively increasing the proteins hydrodynamic radius making the drug bigger and therefore easier to be retained in the blood.

This new polymerisation approach of Chilkoti has overcome many previous problems of PEGylation of drugs such as problems with PEG length and placement of the polymer.

A common disease treated by protein drugs is cancers as they have leaky vessels and are therefore easy targets for these drugs. However previously the protein drugs had such short lifetimes in the blood they couldn’t accumualte efficiently in the tumours. Now with the edition of up to 20nm PEG tails Chilkoti has shown a far better drug efficiency and effect.

This is another scenario whereby the application of nanotechnology has come to the aid of medical science to overcome problems with existing techniques of drug delivery and effectiveness. – CT

Sources : Chilkoti et.al.; Nature

Image: Human breast cancer cell tagged with quantum dots

Cancer Nanomedicine is developing to cover a wide range of applications from imaging, diagnosing to treating cancers with targeted therapies. Cancer Nanomedicine works on the theory that nanometer sized particles of gold, nanomicelles and quantum dots (QDs) have unique functional properties that differ from other available discrete molecules or bulk materials. These nanomaterials when conjugated with other ligands such as monoclonal antibodies, peptides or small molecules can be used to target tumor cells and microenvironment with incredibly high specificity and affinity. Nanoparticles inherently posses a large surface area. Making them ideal for attaching multiple ligands to to create a single nanoparticle that could be used for both tumor imaging and treatment.

There are several barriers that must be overcome before these new methods can be applied clinically:

Firstly the problem of nanoparticle surface opsonisation must be overcome. Nanoparticle surface opsonisation is the process of attaching proteins and other molecules to the surface of the nanoparticle. At present this process is not efficient enough  with surface ‘fouling’ occurring where nonspecific proteins are attaching to the nanoparticles in place of the desired proteins.

Secondly the problem of nanoparticle tissue retention, targeting and tumor penetration must be addressed. These are all processes that are central to manufacturing an effective diagnostic tool and treatment method using nanoparticles.

Finally and very importantly the issue of nonbiodegradable  nanomaterials containing toxic elements must be investigated. Without an idea of the effects that these particles may have on tissue it would be inconceivable to clinically trial these treatments.

New innovative techniques need to be developed to overcome these stumbling blocks on the road to creating a nanoparticle treatment for Cancer.

To read more about this topic get the free article: Futuremedicine

-CT

These nano-delivery systems have become very attractive to researchers because of their ability to infiltrate efficiently into tumour cells. The nano-formulations make use of the leaky more porous blood vessels that supply tumours to accumulate easilyin the tumour cells. This means a higher concentration of drug is delivered efficiently to the tumour cells with a lower dosage administered. This reduces the side-effects associated with systemic chemotherapy administration.

Results showed that the nano-formulation increased the maximum tolerated dose of the drug four-fold compared to the drug by itself. This meant that after one injection it created almost complete tumour regression, whereas the drug by itself would usually have only a modest effect in shrinking the tumours.

Just as importantly the research team have produced a delivery system that is inexpensive and could be used with other drugs, which could be used to increase the effectiveness of other drugs.

The delivery system uses E. coli bacteria which have been genetically engineered to produce an artificial peptide known as chimeric polypeptide. E. coli having been used so often to produce proteins is a very efficient producer of these proteins giving a high yield.

When the drug associates with the chimeric polypeptide it can take on characteristics it doesn’t usually posses. Most drugs do not dissolve in water, which limits their ability to be taken up by cells. Attachment to the chimeric polypeptide allows it to become soluble in water.

The latest experiments using this delivery system involved the use of doxorubicin commonly used in the treatment of blood cancers, breast, ovarian and other cancers.

The team at Duke are now looking at testing the formulation on different cancers in different organs. – CT

Source: Nanowerk

So far due to safety concerns there is only one adjuvant that has been approved for human use in the united states. This is aluminum hydroxide (alum), which is used in vaccines for tetanus and hepatitis B. Still the use of alum will only work with certain diseases and mostly very weakly.

This is where the research team from the Oregon State University step in with their new nanoparticle based adjuvant. There adjuvant is based on nanoparticles prepared with lecithin, which is a common food product.

Lecithin is a group of fatty substances that are found in many animal and plant tissues, most commonly associated with egg yolk. It is regarded as a non-toxic surfactant.

In animal studies lecithin was shown to assist protein antigens to warrant an immune response six times more potent then when alum was used. Moreover it was shown that the lecithin adjuvant allowed a reasonable immune response with only one vaccination jab. Whereas with the use of alum it would take 2-3 shots to warrant the same response.

Based on these results, researchers believe the lecithin nanoparticles adjuvant has great potential for being used in many applications with a good safety profile.

The key issue with designing adjuvants is safety. It is always of the upmost importance that any healthy person receiving a vaccination should not see adverse effects from that vaccine. For this reason the U.S. FDA has always been very conservative with approval of any new vaccine adjuvants.

The belief is that the alum adjuvant has very limited value especially for vaccines against tumors or viruses. By stark contrast the lecithin nanoparticle adjuvant is far more effective. As the incredibly small particles it is made up of can move easily to the lymphatic system, which is key to creating the immune response needed to infer future protection to the individual.

At this time the animal studies have shown that lecithin seems to be tolerated well even more so then alum. If the adjuvant were to be shown safe following clinical trials it could revolutionize vaccine production – CT

Source: Nanowerk

Albumin, a tiny particle found readily in the blood is being used to carry radioactive isotopes to sites of cancerous tumors in the body. With the added benefit of avoiding many of the side-effects of conventional radiotherapies.

In the current issue of the International Journal of Nanotechnology and Biomaterials, Virginia Nazarica Borza et al, from the National Institute of R&D for Physics and Nuclear Engineering in Bucharest, Romania there is a report on the use of human serum albumin nanoshperes being labelled with Rhenium-188 radioisotope.

Previously termed therapies known as ‘magic bullets’ against cancers have been developed for many years. But not since the application of nanotechnology in medicine have the treatments lived up to their name. But now these amazing treatments could be one step closer, as drug delivery direct to the site that requires treatment will increase efficacy of the treatment whilst limiting its side effects. Nanoparticles are the key to this, with their unique chemical and physical properties they can be harnessed to develop such a therapeutic agent.

Borza has shown that these nanospheres can be loaded with our own human albumin attached to radioactive isotopes capable of emitting beta particles. Beta particle decay is in the form of high-energy electrons, which will be given off as the radioactive isotope decays.

The next concern is, of course, the about radioisotopes released inside the body. But not to worry as the team from Romania have worked out the optimal safe parameters for the cancer killing nanospheres. With a high enough radioactivity to destroy the cancerous cells but a short enough half-life to ensure that the radioisotopes do not stay radioactive for too long so that distant tissues do not feel their effects.

The nanospheres are produced in a process involving heating the albumin particles with Rhenium-188, in the presence of a tin salt, a chelating agent, tartate and stannous chloride.

We won’t be seeing this treatment just yet in a clinical setting as the treatment is still at the level of pre-clinical trials to determine their targeting abilities and therapeutic efficacy. But fingers crossed and watch this space! – CT

Source: Nanowerk

A new method to enhance drug delivery has been developed at UC Santa Barbara. The method utilizes a biological system of gaining access to cells.

One of the most difficult barriers to cross in drug delivery is the movement of the drug from the circulation into the tissue. This technique provides a ay of achieving this.

A nanoparticle can be attached to the N-terminus of a peptide, which posses a ‘motif’ that allows it to enter the cell. These motifs consist of amino acid sequences containing arginine and lysine, situated at the peptides C-terminus.

The team at UCSB have specifically targeted prostate cancer cells with this technique but reiterate that the technique can be applied to many different cell and tissue types.

This method of delivering the nanoparticles from the circulation into the tissue will increase the efficiency of drug delivery systems.

With another barrier crossed for successful nanoparticle drug delivery the day we may be able to implement these techniques will draw closer. This may prove to be a huge step towards having a fully functioning nanoparticle drug delivery system. – CT

Source: UCSB

The aim would then be to target the diseased tissues only, limiting any damage you would cause to the healthy neuronal networks of the brain. This is one of the major causes of side-effects seen in cancer sufferers.

The answer is nanomedicine utilizing nanoparticles consisting of inorganic titanium dioxide interfaced with soft biological material. This allows nanomaterials to be put into use for biomedical applications.

What has been demonstrated is that these nanoparticles can be effectively targeted towards a specific target tissue. This was made easier by the fact that brain cancer has a unique receptor that can be targeted giving the treatment its specificity.

The specificity is conferred by the nanoparticles bound soft biological material, which in this instance is an antibody. Antibodies have incredibly specialized binding sites that will recognize a specific protein region known as the antibodies antigen. This allows for the antibodies to bind with high specificity to certain regions of the diseased cells. In this case the antigen is a diseased cells cell surface receptor.

Once the antibody has been bound to its target light can be shone on the nanoparticle. This causes the formation of oxygen free radicals. These free radicals will go into the cell and attack the cell’s DNA and mitochondria (the cell’s every production organelle). Once this is noticed the mitochondria will release chemical messengers to signal the cell to undergo a process of programmed death known as apoptosis.

What was most amazing is that it took only six hours of shining light on the nanoparticles to induce elevated cellular toxicity rates in almost 100% of the cancerous cells. With further enhancement it is foreseeable that you could be diagnosed with cancer and within a few days and some light treatment obliterating most of your diseased cells.

The technique is at the stage of pre-clinical model testing with a view to develop it further for a clinical setting.

What this means, more importantly, is a far less barbaric approach to cancer treatment that doesn’t fall under the slash, poison and burn headings of treatment. Leaving the patient with noticeable side-effects. This may pave the way for treatments that are vastly more effective and at the same time have no side-effects – CT

Source: Science Daily

Researchers from MIT and the University of California have developed nanoparticles (NPs) that are biodegradable, break down readily in the body once the drug payload has been delivered and are easily excreted by the kidneys.

In-vivo tests have so far shown that the NPs can deliver the anti-cancer drug doxorubicin into tumors and can then degrade and be excreted in 1-4 weeks, showing no indications of toxicity.

These tests show a promising future for this kind of drug delivery system. Real headway will be made once it is proven that in the long-term as well as short-term the NP treatment displays no toxicity in the body. – CT

Source: NanoMednet

Paper: Nature Materials

Image of mouse brain tumor using conventional techniques (right) and the fluorescent nanoparticles (left). The Nanopartciles show a much better image of the cerebellar tumor.

Fluorescent Nanoparticles can be injected into a patient, they will localise to the tumor and can be imaged precisely using MRI. This will pave the way for better treatment of brain cancer sufferers. Precise imaging itself will increase patient survival rates as it is so important to succesful treatment of the disease

The next logical step in the fight against brain cancer is to make these fluorescent nanoparticles toxic to the tumor cells. Thereby eliminating the tumor without having to perform invasive surgery.- CT

Source: University of Washington