Colorectal cancer is commonly treated by tumour resection, as chemotherapy and radiation have proven to be less effective, especially if the tumour has metastasized. Resistance to therapies occurs in almost all patients with colorectal cancer, especially in those with metastatic tumours. Cancer stem cells have the ability to self-renew, and their slow rate of cycling enhances resistance to treatment and increases the likelihood of tumour recurrence. Most metastatic tumours are unable to be surgically removed, thus creating a need for treatment modalities that target cancers directly and destroy cancer stem cells. Photodynamic therapy involves a photosensitizer that when exposed to a light source of a particular wavelength becomes excited and produces a form of oxygen that kills cancer cells. Photodynamic therapy is currently being investigated as a treatment modality for colorectal cancer, and new studies are exploring enhancing photodynamic therapy efficacy with the aid of drug carriers and immune conjugates. These modifications could prove effective in targeting cancer stem cells that are thought to be resistant to photodynamic therapy. In order for photodynamic therapy to be an effective treatment in colorectal cancer, it requires treatment of both primary tumours and the metastatic secondary disease that is caused by colon cancer stem cells. This review focuses on current photodynamic therapy treatments available for colorectal cancer and highlights proposed actively targeted photosynthetic drug uptake mechanisms specifically mediated towards colon cancer stem cells, as well as identify the gaps in research which need to be investigated in order to develop a combinative targeted photodynamic therapy regime that can effectively control colorectal cancer primary and metastatic tumour growth by eliminating colon cancer stem cells.

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Photodynamic therapy (PDT) involves interaction of a photosensitizer, light, and molecular oxygen which produces singlet oxygen and subsequent tumour eradication. The development of second generation photosensitizers, such as phthalocyanines, has improved this technology. Customary monolayer cell culture techniques are, unfortunately, too simple to replicate treatment effects in vivo. Multicellular tumour spheroids may provide a better alternative since they mimic aspects of the human tumour environment. This study aimed to profile 84 genes involved in apoptosis following treatment with PDT on lung cancer cells (A549) grown in a monolayer versus three-dimensional multicellular tumour spheroids (250 and 500 μm). Gene expression profiling was performed 24 h post irradiation (680 nm; 5 J/cm2) with zinc sulfophthalocyanine (ZnPcSmix) to determine the genes involved in apoptotic cell death. In the monolayer cells, eight pro-apoptotic genes were upregulated, and two were downregulated. In the multicellular tumour spheroids (250 µm) there was upregulation of only 1 gene while there was downregulation of 56 genes. Apoptosis in the monolayer cultured cells was induced via both the intrinsic and extrinsic apoptotic pathways. However, in the multicellular tumour spheroids (250 and 500 µm) the apoptotic pathway that was followed was not conclusive.

Cancer is a global burden that has prompted extensive research into prevention and treatment, over many decades. Scientific studies have shown that subset of cells within a tumour, known as cancer stem cells (CSCs), are responsible for tumourigenesis, metastasis, drug resistance, and recurrences. CSCs have characteristic features of enhanced self-renewal, proliferation, and limited but multidirectional differentiation capacity. The discovery of CSCs has initiated extensive research into novel cancer treatment regimes. Evidence indicates that CSCs are resistant to conventional chemo- and radiation therapy leading to treatment failures, cancer metastasis, secondary cancer formation, and relapse. Because of the observed phenomena in the course of cancer prognosis, a need for treatment modalities targeting CSCs is important. Photodynamic therapy (PDT) is a clinically approved, minimally invasive, therapeutic procedure that can exert a selective cytotoxic activity toward cancerous cells while reducing toxicity to normal cells. It uses a photosensitizer (PS) that becomes excited when subjected to light at a specific wavelength, and the PS forms reactive oxygen species (ROS) killing malignant cells. Currently, PDT is being investigated as a target specific treatment for CSCs by the addition of carrier molecules and antibody conjugates bound to the PS. Targeted PDT (TPDT) may be able to not only eradicate the tumour mass but kill CSCs as well.