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Most method emerged as new frontier in

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Most lethal cancers are associated with
distant metastatic spread and often require chemotherapy, radiation therapy,
immunotherapy and hormonal therapy among other systemic treatments. Although regarded
as effective measures of destroying rapidly metastasizing cancer cells, these
treatments often do a lot more to the body, than just cure cancer. Serious side
effects frequently accompany these therapies, mainly because of their
non-specific targeting nature, that result in the destruction of healthy cells,
besides the regular cancer cells. This is particularly perilous when the cancer
originates in bone marrow, which is a niche of haematopoietic stem cells and
therefore it becomes quite challenging for chemotherapeutic drugs to target and
selectively destroy the cancer cells.

    In
contrast, photodynamic therapy or phototherapy (PT) involves a non-invasive
procedure for destroying cancer cells, specifically targeting the cancer cells
via a precise spatiotemporal control. Traditional phototherapy, as the name
suggests, utilizes light from external sources to activate the photosensitizer
drugs, leading to cell death. This method emerged as new frontier in treating
skin cancers but the problem arises in case of deep-seated tumours. In such
cases, external light cannot penetrate the skin and reach the underlying
tissues due to their being absorbed and scattered by the tissue system. Due to
the limited penetrance of external light, PT has been useful in treating only surface
lesions.

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To overcome this limitation, researchers at
the Washington School of Medicine have designed a set of experiments to prepare
an optimized system that uses Cerenkov Radiation (CR)-mediated conversion of
chemotherapeutics to phototherapeutics. An orthogonal cancer targeting strategy
using nanomicelles was developed. Targeted delivery of a radionuclide and the
drug is necessary to enable co-localization and subsequent CRIT (Cerenkov
Radiation Induced Therapy).The radionuclide used in this case is 18-FDG which
enters cancer cells through overexpressed Glut transporters  on cancer cells. 18-FDG acts as a point
source of photoelectronic energy and can stimulate any photoactive material in
its close proximity. It was used to photoactivate titanocene (the
photosensitizer) through Cerenkov radiation, causing cell death. Titanocene
enters the cancer cells through the alpha-4-beta-1 receptors on the cell
surface. The combination of  alpha-4-beta-1
and Glut receptors is not expressed in any healthy haematopoietic cell in the
bone marrow, hence they remain unaffected.

The CRIT thus transforms chemotherapeutic
drugs to phototherapeutic ones using radionuclides that emit cerenkov radiation
and offers a non-invasive technique of treating a large number of previously inaccessible
deep-seated rapidly growing cancer cells; it will definitely be a boon for a
number of cancer patients who need to undergo regular chemotherapy and
radiation-induced therapies so as not to succumb to the deadly disease.

 

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