Question

Describe some of the different ways that RADIOTHERAPY could be functionalized to accumulate in ORAL CANCER tissue. Would it be more beneficial to perform active or passive targeting? If you were to perform active targeting, what are 3 different tissue biomarkers you would try to target, and why? What sorts of targeting molecules would you put on the surface of Gold nanoparticles ? What are your most important considerations when picking targeting molecules (size, charge, affinity, etc)? How do you expect this active targeting to change your overall nanoparticle accumulation in your tissue? If you were to perform passive targeting, what physical properties of your nanoparticle would you optimize, and why? How do you expect this passive targeting to change your overall nanoparticle accumulation in your tissue?

Answer 1

Oral cancer is normally a curable cancer if it is diagnoised at the early stage. A oral cancer is usually a sore in mouth that does not heal or pain that does not go beyond 3 weeks. Treatment of oral cancer involves radiation therapy or chemotherapy or surgery . In extreme cases both chemotherapy and radiation therapy is combined with surgery and this is called adjuvant therapy. In some cases radiation therapy is used before surgery and it is called neoadjuvant therapy. The following are the types of radiation therapy.

1.External beam radiation therapy.

In this method a machine containing the radiation is directly pointed from outside to the target area. This is the commonly used radiation therapy. Doctors are very careful while performing this procedure such that normal cells are not damaged and only the target area is pointed direct to the beam of radiation. Inorder to save the normal cells from radiation hazard they often prefer smaller doses. This therapy is usually painless and has severe side effects. Usually this treatment lasts for 5 days or a week. The doses can also be given in the following ways.

Hyperfractionation - here the doses are given in larger number for one day.

Accelerated fractionation - here the doses are given in small amounts for 3 or 4 days.

Intensity modulated radiation therapy is a new method of external therapy that is widely used now a days. Here the beam is focused by computer programs or other sources such as MRI for mapping the cancer location. The radiation is delivered precisely to the tumour location.

Internal Radiation therapy

It is a type of radiation therapy whereby radiation material is directly inserted near the site of cancer. It is also called as Brachytherapy. The radiation material is usually in form of pellets and it is placed at cancer site.

2. Active targeting is normally prefered than passive targeting as there are less side effects and deliveryu of radiation particles are efficient.

3. Active trageting is achieved by conjugating a nanoparticle and a targetting component such that nanoparticle gets accumulated in the tumour site. This is achieved by specific interactions like

1. Lectin- carbohydrate interaction - Lectins are proteins of non immunological origin that detects glycoproteins on call surface.

2.Ligand - Receptor interaction

3.Antibody- antigen interaction.

4. Gold nanoparticles are usually conjugated with antibodies specific to that area of cancer site.

5. The most important consideration is affinity of the antiibody to that antigen in that particular target site and size of the particle. The size of the particles will also vary and in most cases the size will be uniform. Their size varies from 1nm to 100nm . In some cases 1micrometer nanoparticles are also used as it produced less side effects. The result is optimized by delivering different size of nanoparticles.

6. The active targeting of gold nanoparticles facilitating receptor mediated endocytosis realesing the theraputic agent inside the target cell. Usually Gold nanoparticles are conjugated with a drug eg cetuximab and gemcitabine in pancreatic cancer. By active targeting machnism the theraputic efficiency is more and it is less toxic compared to other methods. Normal cells remain unaffected by this method.

7. In passive targeting, Smaller size enables larger upatke of the theraputic agent by the target cell because the smaller size has larger surface area to volume ratio such that more drug will be released at the target site. More over the nanoparticles are coated with hydrophilic polymers or surfactants or biodegradable polymers like PEG such that the nanoparticle will be present in blood stream for more longer time and the host immune system cannot recognise .

8. The theraputic agent is delivered to the target site by enhanced permeation and retention effect. In this method the theraputic agent is delivered near the target site and not into the target cell. The vascularisation of the cell will be laeky due to disruption of gapjunction and hence the drug will surround the tumour by enhanced permeation method. The drug will be in action for longer time Usually liposomes are also used in passive targeting. It has many limitations compared to active targeting.