Cell Death Pathways and Phthalocyanine as an Efficient Agent for Photodynamic Cancer Therapy

Abstract

The mechanisms of cell death can be predetermined (programmed) or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS) are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT) uses non-toxic chemotherapeutic agents, photosensitizer (PS), to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs) are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events.

Photodynamic Therapy, a Potential Therapy for Improve Cancer Management

“…Apoptosis is a highly regulated and programmed cell death response that comprises interdependent and synchronized pathways [58,59]. Photodamage-mediated permeabilized mitochondrial membranes induce leakage of apoptogenic proteins, such as cytochrome C. In return, the released apoptogenic proteins activate the caspase mediated apoptotic pathway [60,61]. Photodamage may also lead to the induction of other apoptotic pathways [62,63].…”

Nano-Mediated Photodynamic Therapy for Cancer: Enhancement of Cancer Specificity and Therapeutic Effects

“…This family of tetrapyrrolic structures with incorporated central metal ions, is also used for treatment of noninvasive cancers, and designated as a second generation of PSs with improved photophysical and photodynamic properties over those of porphyrins. These tetrapyrrolic macrocycles strongly absorb light in the near-infrared region of the visible spectrum and prove to effectively kill malignant tumors during PDT [41][42][43]. One of the major downfalls of this family of PSs is the lack of adequate water solubility, such issue can be overcome by adding charged particles, carbohydrates or peptide ligands to the periphery of phthalocyanines to give rise to third generation PSs [43].…”

Photoactivated drug delivery and bioimaging

“…Moreover, it is also worthy to notify that such visible light‐activated process has been also investigated in photodynamic therapy (PDT) study, one particular anticancer treatment involving in the usage of photosensitizers (PS) to generate reactive oxygen species (ROS) upon light exposure at a suitable wavelength. These ROS demonstrates effective cytotoxicty and would be able to destroy tumor cell structures, and thus achieve the targeted cell death in vitro and in vivo . So far, some PS molecules have been found to respond to visible light irradiation and have already been applied for visible light‐activated PDT.…”

“…These ROS demonstrates effective cytotoxicty and would be able to destroy tumor cell structures, and thus achieve the targeted cell death in vitro and in vivo. 52 55 In this rational design, the AuNPs could also act as photocatalyst, which can generate active radical species, e.g., O˙2 or OH˙, under visible light illumination to cleave the linkage group between AuNPs and TiO 2 nanotube. So the payload molecules inside the TiO 2 nanotube could diffuse into the surroundings and exhibited the promising drug activity.…”