Triarylboron-Based High Photosensitive Probes for Apoptosis Detection, Tumor-Targeted Imaging, and Selectively Inducing Apoptosis of Tumor Cells by Photodynamics
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Abstract
<p class="first" id="d2460882e125">Herein, a series of triarylboron-based fluorescent
probes were developed for distinguishing
apoptosis from living cells and even necrosis. They also demonstrate high photosensitivity
because they can produce detectable reactive oxygen species (ROS) under an ultra-low
light power density (1.5 mW/cm2). By changing the peripheral groups to regulate the
performance, we identified a multifunctional probe, TAB-6-amyl, which can be used
not only for selectively imaging apoptosis but also for the targeted imaging of SKOV-3
cells in vitro and in vivo. It could further specifically induce the apoptosis of
SKOV-3 cells under light irradiation. During the study, we also found that TAB-6-amyl
can cross the blood-brain barrier (BBB). Therefore, another probe based on this kind
of structure, TAB-5-M-1-cRGD, was constructed for the targeted imaging of brain glioma
cells and inducing their apoptosis. This study offers some promising tools for apoptosis
detection and tumor photodynamic therapy (PDT).
</p>
The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.
Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.
[1
]School of Pharmacy and Institute of Pharmacy, North Sichuan Medical College, Sichuan
637100, China
[2
]Thyroid and Breast Surgery, Affiliated Hospital of North Sichuan Medical College,
Nanchong 637000, People’s Republic of China
[3
]Institute of Chemistry & University of Chinese Academy of Sciences, Chinese Academy
of Sciences, Beijing 100190, China
[4
]College of Chemistry and Chemical Engineering & Chongqing Key Laboratory of Theoretical
and Computational Chemistry, Chongqing University, Chongqing 401331, China
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