**3. Photodynamic therapy an unconventional treatment for CRC**

Photodynamic therapy (PDT) is a promising unconventional treatment method for CRC (**Figure 1**) [8].

PDT treatment is a coordinated process, which begins with the intravenous administration of a photosensitizer (PS) drug [8]. Once the PS drug enters the blood stream it is then either passively or actively absorbed in tumor site, depending on the PS drug delivery mechanism that is involved [26]. Within standard conventional PS drug delivery mechanisms the advantage is that the PS drug tend to preferentially localize in diseased tissue via the enhanced permeability retention (EPR) effect and so is passively absorbed, promoting PDT induced tumor destruction with only slight healthy tissue damage [26]. However, current research studies are focused on improving PS passive drug uptake via chemical or functional modifications in order to promote a more specific and actively targeted PS delivery in cancer cells only, so that photosensitivity, localized healthy tissue destruction and other additional unwanted side effects can possibly be eliminated [26]. Since, PS drugs are light absorbing molecules their activation is achieved when they are

### **Figure 1.**

*PDT treatment of CRC. PS drugs are administered to a patients CRC tumor site via a colonoscopy endoscope, whereby they localize in targeted tumor cells. Laser light irradiation is then also administered to the target tumor site via a colonoscopy endoscope, whereby it penetrates the large intestines tissues/tumor and activates the PS. The PS then undergoes a photoreaction to produce ROS and/or singlet oxygen, which in turn induces cytotoxic cell death in CRC tumor tissues.*

**45**

**Figure 2.**

*Targeted Photodynamic Therapy as Potential Treatment Modality for the Eradication of Colon…*

exposed to laser irradiation light at a specific wavelength [26]. Thus when a tumor (which contains the localized PS drug) is exposed to laser irradiation light, the PS absorbs the photons and becomes excited [2]. This excitation promotes the PS from a ground state to a higher level of energy known as a singlet state [27]. This singlet state is very short lived and PSs return to their ground state rapidly after losing their energy to fluorescence or internal heat conversion [27]. However, the singlet state PS may also convert to a triplet state via intersystem crossing, resulting in an electron spin change, which if reacted with molecular oxygen (as found in cells), it will give rise to free reactive oxygen species (ROS), which can result in tumor

Since the colon can be easily accessed via the rectum opening of the large intestine using an endoscope, this form of oncological PDT treatment for CRC tumors is possible [8]. Studies by Hodgkinson et al. [2] and Kawczyk-Krupta et al. [8] have noted that the PDT treatment of CRC which are inoperable, have only slightly advanced lesions/polyps or massive advanced tumors is a safe and feasible treatment option. Thus, colonoscopy endoscopes are used to directly deliver PS drugs to target tumor regions, as well as administer the required wavelength of laser

The overall ability of PDT to successfully destroy cancer cells depends of the efficacy of ROS production in target cells. ROS can be produced via two different types of photoreactions (**Figure 2**) [26]. Within photoreaction type I, the PS drug reacts with surrounding cellular biomolecules via a hydrogen atom electron transfer to form free radicals, which react with cellular molecular oxygen, generating ROS, which in turn induces oxidative stress in target cells and so destroys them [27]. Whereby within photoreaction type II, the PS drug reacts directly with molecular oxygen in the cell to form singlet oxygen species, which are able to oxidize various substrates within target cells and so induce cell death [27]. When ROS and singlet oxygen species are generated from a PDT reaction, they are cytotoxic and so oxidize various substrates in a tumor cell inducing stress that triggers various cell death pathways such as apoptosis, autophagy or necrosis. Both types of photoreactions may occur simultaneously, however type I reactions generally favor apoptotic death in tumor cells [28]. Additionally, the effectivity of both photoreaction pathways depends on the type of

*PDT photophysical and photochemical mechanism of action for PS drug activation in tumor cells. When a PS drug is activated at a specific wavelength of light it becomes excited and so reacts with either molecular oxygen or other substrates within the surrounding areas of a cell, generating ROS, which in turn induces oxidative stress* 

*in cells triggering various cell death pathways and overall tumor destruction.*

*DOI: http://dx.doi.org/10.5772/intechopen.84760*

irradiation light to activate a PS drug [2, 8].

destruction [27].
