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Photodynamic therapy (PDT) is a therapeutic method that enables the selective destruction of cancer tissue. PDT is complementary to traditional cancer treatment approaches, such as radiotherapy, surgery and chemotherapy. The basis of PDT is a photodynamic reaction that consists of three components: the drug-photosensitizer, light of an appropriate wavelength and oxygen. The photodynamic reaction involves the light-induced generation of an excited state in a photosensitizer molecule (PS). Before excitation with light, the PS remains in its singlet state. After illumination, the PS undergoes a transition from its low-energy ground-singlet state to a higher energy state, known as the singlet-excited state. In the excited state, the PS may further undergo intersystem crossing, where the short-lived singlet state is converted into an excited triplet state, which is relatively long lived. In this state, the electrons have a parallel spin in the orbital and can react by three different mechanisms. In Mechanism I, the excited PS interacts with a cellular molecule, transferring a proton or an electron to the molecule, which forms a radical. The modified molecule can react with oxygen and form reactive oxygen species (ROS). It is worth noting that water molecules can also be a target for the attack of PS with the formation of hydroxyl radical and superoxide anion radical. In Mechanism II, the energy of the triplet state PS is transferred directly to molecular oxygen, generating highly reactive singlet oxygen. Another mechanism of the photodynamic reaction is Mechanism III, which is based on the direct interaction of the excited PS on the target cancer cells without ROS formation (1-3).
PDT can initiate a plethora of molecular effects in the cancer tissue. Also, it can lead to vascular damage, described as vascular shutdown, as well as induce inflammation and other tumor-specific immune reactions (4). PDT can result in a variety of cellular changes (5). These changes include an increase in the intracellular Ca2+ concentration and the activation of phospholipase A2,downregulation of EGFR at the cell surface,de novo accumulation of ceramide that leads to the increase in mitochondrial membrane permeability and release of cytochrome c,expression of IL-6and damage of integrins. The cytotoxicity caused by PDT is mediated via apoptosis, necrosis and possibly autophagy.
Liposomal photodynamic therapy
Photosensitizers used currently in clinical...