Photodynamic Therapy as an Emerging Treatment Modality for Cancer and Non-Cancer Diseases

Abstract

Hu et al., J Anal Bioanal Tech 2014, S1 http://dx.doi.org/10.4172/2155-9872.S1-e001 ISSN: 2155-9872 JABT, an open access journal Photodynamic Therapy-Cancer J Anal Bioanal TechPhotodynamic therapy (PDT) is a treatment modality involving photoactivatable chemicals (called photosensitizers), light and tissue oxygen [1][2][3][4][5][6]. PDT has clinical applications in the treatment of a variety of solid cancers [4,7-21], including but not limited to those of lung, skin, breast, head and neck, digestive tract, pancreas, liver, bladder, ovary, prostate and brain. In addition, there are many clinical applications of PDT for treatment of a wide range of non-cancerous conditions, such as bacterial and fungal infections; hyperproliferative or inflammatory conditions, such as macular degeneration or psoriasis; and premalignant conditions, such as actinic keratosis [22] and Barrett's esophagus [23]. To achieve better therapeutic efficacy, new photosensitizers and novel light sources are continuously being developed, and the mechanisms of action are becoming better understood [24,25]. To achieve improved tumor selectivity and to reduce side effects in the treatment of cancer, the concept of targeted photodynamic therapy has been successfully developed by attaching specific functionalities to the photosensitizer, such as antibodies recognizing tumor antigens [26,27], or ligands and peptides to recognize receptors [28], which could be selectively expressed on one of the two major tumor compartments, either on the malignant cells or on tumor neovasculature. To achieve better efficacy than PDT that is targeted to a single tumor compartment (stPDT), a recent editorial [29] in this Journal summarized a new PDT approach (Figure 1), which was designed for dual targeting of photosensitizers (dtPDT) to both malignant cells and neovasculature [30,31] by conjugating photosensitizers to a protein, factor VII, the natural ligand for tissue factor. This approach allows for dual targeting of malignant cells and of tumor neovasculature, both of which either overexpress or selectively express tissue factor [30][31][32][33], respectively.In this special issue on PDT-Cancer, PDT scientists and experts worldwide contributed seven peer-reviewed articles. These review and research articles broadly cover the use and applications of PDT for cancer, for infections and for inflammatory conditions. Menon and Stafinski [34] in Canada thoroughly reviewed reports of clinical applications and clinical trials of PDT for the treatment of different types of cancers that were published in English between January 1997 and June 2011. They summarized a total of 266 studies, which involved 11,427 patients and 34 different types of cancer in diverse organs, such as anal and perianal cutaneous cancers, as well as cancers of the bile duct, bladder, brain, breast, cervical, esophageal, eye, gastrointestinal, head and neck, lung, peritoneal cavity, colorectal, liver, ovary, pancreas, prostate, skin, vulva, etc. Tsipursky, Churgin, Conway and Peyman [35] in the Uni...

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

“…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 PS drug administered, where is localized in the tumor cell, as well as the amount of molecular oxygen present within the tumors microenvironment [29].…”

“…PS drugs generate cytotoxic ROS or singlet oxygen species when they become activated at a particular wavelength, which in turn induces physical or chemical damage in target tumor cells [28]. In relation to the activation of PS drugs for effective PDT, it is important that they have a high molecular absorption coefficient within the red spectrum of light (650-780 nm), as to ensure maximum light absorption for PS excitation (as some endogenous human body pigments can absorb light), warrant minimal patient photosensitivity before treatment, as well as guarantee deep tissue penetration in target tumor sites [32,33].…”

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

“…In 2014 Hu et al presented an approach towards the dual targeting of both neoplastic cells and the tumour neovasculature at the same time using newly designed PSfactor VII conjugates that selectively bind to overexpressed tissue factor [8]. An alternative approach for the localized PS delivery is the use of a relatively easy to use portable "fiber optic-based sensitizer delivery" device which has recently been successfully tested on ovarian cancer cells.…”

“…The latter also protects the drugs from enzymatic or macrophagic digestion before reaching its target site. Gold nanoparticles, peptides, proteins such as transferrin, EGF or insulin, low density lipoproteins (LDL), folic acid, carbohydrates, somatostatin and liposomes have also been considered as delivery vehicles for PSs [5,8,61]. Some groups suggest that an ideal drug delivery system should ensure the PS delivery into the cell nucleus from where it would have a more detrimental effect compared with PSs that accumulate in the plasma membrane (such as porphyrins), Golgi or mitochondria.…”

“…The highly reactive oxygen species (ROS) have the ability to locally destroy cancerous tissue in a patient [4,5,[7][8][9][10][11][12]. In the clinic PDT treatment commonly consists of two stages ( Figure 1B).…”