Photodynamic Therapy for Cancer: Principles, Clinical Applications, and Nanotechnological Approaches

Abstract

Photodynamic therapy (PDT) is based on photochemical processes between light and an exogenous photosensitizer (PS) localized at disease level. These components, tolerated singly by the cells, generate cytotoxic oxygen-based molecular species in proper dosage and concentration. Mechanistically it consists in three phases: excitation of PS, generation of toxic oxygen species, and cell death ( Fig. 5.1 ). In the fi rst phase, light of an appropriate wavelength, usually visible (VIS) or near-infrared (NIR), excites the PS molecules from the ground state to the excited singlet state. The radiation wavelength is usually chosen to coincide with the maximum absorption wavelength of the drug molecule. In analogy with many other fl uorescent molecules, PS can, at this stage, decay to its ground state with concomitant emission of light in the form of fl uorescence. On the other hand, the excited singlet state PS may also undergo a process known as intersystem crossing whereby the spin of the excited electron inverts to form a relatively more stable and long-lived excited triplet-state that has electrons which spin in a parallel conformation in the two highest occupied molecular orbitals. High quantum effi ciency for this transition is a key characteristic of a good PS. The PS in triplet state can either decay to the ground state or transfer electron/energy to the surroundings through two types of reactions. A type 1 process

Co-delivery of Docetaxel and Disulfonate Tetraphenyl Chlorin in One Nanoparticle Produces Strong Synergism between Chemo- and Photodynamic Therapy in Drug-Sensitive and -Resistant Cancer Cells

“…These differences highly complicate and make unlikely that the free drug combinations reach the target site at optimal ratios guaranteeing synergistic effects. However, the use of multifunctional nanocarriers that accommodate in their structure more than one drug at a fixed ratio appears a unique opportunity to overcome this problem. − …”

Multifunctional mesoporous silica nanoparticles as efficient transporters of doxorubicin and chlorin e6 for chemo-photodynamic combinatorial cancer therapy

“…ROS, mainly singlet oxygen ( 1 O 2 ), is cytotoxic and capable of killing cancer cells nearby. 16,17 However, the application of many PSs clinically has been limited by their nonspecific damage to normal tissues and poor water solubility, which also highly reduce PDT efficacy. Covalently incorporating PSs with MSNs could greatly enhance their solubility and particularly improve the accumulation in the tumor tissue.…”

Hyaluronan-decorated polymer nanoparticles targeting the CD44 receptor for the combined photo/chemo-therapy of cancer

“…[1][2][3] This approach has been found promising when photodynamic therapy (PDT) is combined with conventional chemotherapy in the management of several types of cancer. [4][5][6][7] In PDT a photosensitizer (PS), after irradiation at a specific wavelength, causes mainly the formation of the cytotoxic singlet oxygen ( 1 O 2 ) which reacts with tissue components, leading to cell death through the initiation of apoptosis and necrosis. 8 Indeed acting by different mechanisms, cytotoxic drugs can act in concert with PS for tumor killing, achieving potentiated therapeutic outcome through an anticancer synergistic effect.…”