Why Nanotechnology Is Important - pg. 2

Benefits for treatment and clinical outcomes

Cancer therapies are currently limited to surgery, radiation, hormone and chemotherapy. All four of these methods risk damage to normal tissues and sometimes incomplete eradication of the cancer. Nanotechnology offers a way to aim therapies directly and selectively at just cancerous cells.

Nanocarriers

Conventional chemotherapy uses drugs known to kill cancer cells effectively. But these cytotoxic drugs kill healthy cells in addition to tumor cells, leading to adverse side effects such as nausea, neuropathy, hair loss, fatigue, compromised immune function and possible damage to the heart and other organs.

Nanoparticles can be used as drug carriers for chemotherapeutics that deliver medication directly to the tumor or its blood supply, while sparing healthy tissue.

		This image depicts "nanoscale" devices that find and destroy blood vessels that supply nourishment to tumor cells while leaving blood vessels in healthy tissue unharmed.
Image courtesy of the Center for Cancer Nanotechnology Excellence at UC San Diego and the UCSD Moores Cancer Center

Nanocarriers have several advantages over conventional chemotherapy. They can:

• Protect drugs from being degraded in the body before they reach their target
• Enhance the absorption of drugs into tumors and into the cancerous cells themselves
• Allow for better control over the timing and distribution of drugs to the tissue, making it easier for oncologists to assess how well they work and
• Prevent drugs from interacting with normal cells, thus avoiding side effects

Passive targeting

There are now several nanocarrier-based drugs on the market that rely on passive targeting through a process known as "enhanced permeability and retention." Because of their size and surface properties, certain nanoparticles can escape through blood vessel walls into tissues.

In addition, tumors tend to have leaky blood vessels and defective lymphatic drainage, causing nanoparticles to accumulate in them: this concentrates the attached cytotoxic drug where it's needed, protecting healthy tissue and greatly reducing adverse side effects.

Active targeting

Nanoparticles are being developed that will actively direct drugs to cancerous cells, based on the molecules that they express on their cell surface. Molecules that bind to particular cellular receptors can be attached to a nanoparticle so that they actively target cells expressing the receptor.

Active targeting can even be used to bring drugs into the cancerous cell, by inducing the cell to absorb the nanocarrier. Active targeting can be combined with passive targeting to further reduce the interaction of carried drugs with healthy tissue achieving greater tumor reduction using lower doses of the drug.

Destruction from within

Moving away from conventional chemotherapeutic agents that activate normal molecular mechanisms to induce cell death, researchers are exploring ways to physically destroy cancerous cells from within.

One such technology has used 'nanoshells' in the laboratory to thermally destroy tumors from the inside. A nanoshell consists of beads that are about three millionths of an inch wide, with an outer metal wall and an inner silicon core.

Nanoshells can be designed to absorb light of different frequencies, generating heat (hyperthermia).

	Once the cancer cells take up the nanoshells (via active targeting), scientists apply nearinfrared light that is absorbed by the nanoshells. This creates intense heat inside the tumor that selectively kills tumor cells without disturbing neighboring healthy cells.
Image courtesy of the National Cancer Institute

Similarly, targeted magnetic nanoparticles are in development that will not only be visible when using Magnetic Resonance Imaging (MRI), but also destroy cells by using hyperthermia.

Examples of approved nanotechnologies for cancer

Liposomes, which are first generation nanoscale devices, are being used as drug delivery vehicles in several products. For example, liposomal amphotericin B is used to treat fungal infections often associated with aggressive anticancer treatment.

Image courtesy of Dr. Kosi Gramatikoff

The medication Doxil also uses liposomes: liposomal doxorubicin is used to treat certain myeloma and ovarian cancers. Doxil takes the active chemotherapy drug doxorubicin and places it into a liposome and another layer of hair-like strands made from a rubber called methoxypolyethylene glycol.

This coating allows Doxil to evade detection and destruction by the immune system thus increasing the time the drug is in the body. At least 90 percent of the drug stays inside the liposome while in the blood. As a result, Doxil has more time to reach the tumor tissue where the medication slowly leaks out.