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Nanoparticles find favour in diagnosis, therapy

Nanomedicine is very powerful because a single protein inside a living cell can be tracked

Nanomedicine involves the design, manufacture, administration, and monitoring of drugs and diagnostic/therapeutic devices that use nanoparticles about 1-100 nanometres in size. (1 nm = 10{+-}{+9} m, a strand of human hair is 80,000 nm thick and a red blood cell is 5000 nm in diameter).

The nanoparticles exhibit properties (strength, electrical conductivity, elasticity, colour etc.) that same materials do not have at micro or macro sizes.

Bioavailability

The efficacy of any drug depends strongly on its bioavailability — referring to the presence of the drug in the part of the body where it is needed.

Drug delivery mechanisms focus on increasing bioavailability and the residence time.

Nanoparticles do both. Generally they assist in diagnosis (as contrast agents in ultrasonography, MRI imaging), delivery (by residing for a long time), treatment (by penetrating through cell walls and into cytoplasm inside the nucleus of the cell), accessing areas (crossing blood-brain barrier) and stimulating the body’s innate repair mechanism. Quantum dots are nanoparticles that glow when exposed to ultraviolet light. They shine longer and brighter than today’s fluorescent dyes, and are used, both in vitro and in vivo, as luminescent tags to track proteins.

Detecting cancer

This is very powerful because a single protein inside a living cell can be tracked. As the colour of a nanoparticle depends on its size (2 nm size particles glow bright green and 5 nm particles appear dark red) different proteins in a cell can be detected (for each has a colour).

Cancer is detected using the amount of specific proteins (also called biomarkers) in the blood. Using nanoparticles, as few as 100 molecules of Prostate Specific Antigen (PSA), or Cardiac Troponin I [cTnI] in a drop of blood can be detected.

Cadmium selenide quantum dots seep into malignant tumours and assist doctors in identifying their location and size.

Nanosphere Inc. has developed ‘Verigene system’, that, according to its web site, “uses gold nanoparticles (13-20 nm diameter) functionalised with either a defined number of antibodies that are specific to a particular protein of interest” to detect proteins in blood.

In photodynamic therapy, gold coated nanoshells, 120 nm diameter, have conjugating antibodies/peptides that make them get attached to cancerous cells.

When a tumour is irradiated by infrared laser, gold gets heated thereby killing the cancer cells.

Dendrimer is a synthetic molecule with branches (emanating from a core) and having hooks that can latch onto cells. Folic acid is attached to a few of the hooks, and anti-cancer drugs to others.

The carcinogenic cells easily absorb the folic acid and along with it the drugs enter the cells. This is targeted delivery without harming the good tissue.

Antiemetic drugs

Nanometre sized particles of pharmaceutical compounds (produced using a proprietary technology) are used to manufacture antiemetic and other drugs (to treat high cholesterol, anorexia, cachexia, and during renal transplant).

One product that treats ovarian cancer uses a liposome to encapsulate the drug to prevent “detection and destruction by immune system.”

Another combines the active ingredient with a natural protein called albumin into a nanoparticle 1/100th the size of a red blood cell, to cross cell walls of a tumour.

Chemotherapy-induced nausea and vomiting or postoperative nausea and vomiting is prevented by an antiemetic based on nanotechnology.

Blood-brain barrier

Unlike conventional antiemetic which targets nausea and vomiting signals in the gut, this works by crossing the blood-brain barrier and antagonising the NK1 receptors in the brain thereby preventing the occurrence of a vomiting reflux.

However, it does not affect other receptors such as serotonin, and dopamine. Tissue removed by surgery must be replaced by growing new cells.

For this a biocompatible and biodegradable scaffolding of nanostructured polymer is “seeded” with cells taken from the patient. The cells regenerate fast and the scaffolding slowly dissolves. Peptide Amphiphiles assist in cell growth and are used to treat bone injuries.

Nanoscale materials are used for developing synthetic bone and coating artificial joints.

Silver kills microbes by preventing the transport of electrons and cell replication. Hence nanocrystalline silver is used as an antimicrobial coating on wound dressings and catheters.

The toxicity of nanomaterials over long periods is yet to be determined. Due to their unusual properties, the toxicity data corresponding to large scale particles cannot be extrapolated.

The high reactivity (due to large surface) and high mobility (due to size) may cause high toxicity.

The increase in bioavailability warrants close monitoring. The impact on cellular and tissue functions, path traversed in the body, and unknown reactions are also areas of concern.

Many quantum dots are toxic, but studies have shown that protective coatings may eliminate toxicity.

S. CHELLAIAH

(The author is Consultant, Satyam Computer Services Ltd. Email: chellaiah_s@satyam.com )

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