Photodynamic Therapy Induced Cell Death Mechanisms in Breast Cancer

Abstract

Breast cancer is the second most common cancer globally and the pioneering cause of mortality among women. It usually begins from the ducts or lobules, referred to as ductal carcinoma in situ, or lobular carcinoma in situ. Age, mutations in Breast Cancer Gene 1 or 2 (BRCA1 or BRCA2) genes, and dense breast tissue are the highest risk factors. Current treatments are associated with various side effects, relapse, and a low quality of life. Although conventional treatments, such as surgery and chemotherapy, have been used for decades, their adverse side effects on normal cells and tissues pose a major weakness, which calls for a non-invasive treatment option. Photodynamic therapy (PDT) has proven to be a promising form of cancer therapy. It is less invasive, target-specific, and with reduced cytotoxicity to normal cells and tissues. It involves the use of a photosensitizer (PS) and light at a specific wavelength to produce reactive oxygen species. One of the reasons for the target specificity is associated with the dense vascularization of cancer tissues, which tends to increase the surface area for the PS uptake. Photosensitizers are light-sensitive molecules, which result in cancer cell destruction followed by light irradiation. Depending on the localization of the PS within the cancer cell, its destruction may be via apoptosis, necrosis, or autophagy. This review focuses on the breast cancer etiopathology and PDT-induced cell death mechanisms in breast cancer cells.

Photoactivation of Chemotherapeutic Agents with Cerenkov Radiation for Chemo-Photodynamic Therapy

“…The presence of PS in nucleus, ER, and mitochondria can induce apoptosis. 1 According to the Nomenclature Committee on Cell Death (NCCD), more cell death mechanisms have been proposed: mitotic catastrophe, piroptosis, parthanatos, necroptosis, and ferroptosis. 42 However, these mechanisms have been poorly evaluated in PDT.…”

“…For example, if the PS is in endoplasmic reticulum (ER), it can induce autophagy, or necrosis when it is on cell membrane. The presence of PS in nucleus, ER, and mitochondria can induce apoptosis . According to the Nomenclature Committee on Cell Death (NCCD), more cell death mechanisms have been proposed: mitotic catastrophe, piroptosis, parthanatos, necroptosis, and ferroptosis .…”

“…Although chemotherapy (CMT) is widely applied in clinical practice, it has limitations, such as low therapeutic effects and systemic toxicity. Combining treatments, such as CMT + photodynamic therapy (PDT), produces a more effective synergistic therapeutic response than individual therapies. , For example, Sun et al developed an aptamer@SPION nanosystem for co-delivering a chemotherapeutic agent and a photosensitizer molecule . The significant decrease of cell growth under light irradiation of the nanosystem mainly resulted from the chemo-photodynamic synergistic effects …”

“…The 3 PS* can go to the 0 PS state by (i) emitting light (phosphorescence), (ii) energy transfer to molecular oxygen (O 2 ) (type II reaction), or (iii) by electron or proton transfer to biomolecules or O 2 present in the tissue (type I reaction). When the type II reaction occurs, 1 O 2 is formed, while the type I reaction produces free radicals that react with O 2 and form ROS, mainly the anionic radical O 2 * − , the precursor of H 2 O 2 and the hydroxyl radical (HO • ). All these species attack other molecules through a chain of reactions that are highly cytotoxic to cells.…”

Hybrid Inorganic-Organic Core-Shell Nanodrug Systems in Targeted Photodynamic Therapy of Cancer

“…PS agents in PDT commonly follows one or more of the three different pathways to cause death on cancer cells, namely necrosis, apoptosis, and autophagy [87]. Typically, the response of PDT on the cell death pathway may vary depending on the cell type, the PS agent, its subcellular localization and total fluence delivered [35,88]. However, the main instigator in PDT is the cytotoxic singlet oxygen that is responsible for initiating reactions and the activation of cell death pathways [35,89].…”