Apoptosis Following Photodynamic Tumor Therapy: Induction, Mechanisms and Detection

Plaetzer, Kristjan; Kiesslich, Tobias; Oberdanner, Christian Benno; Krammer, Barbara

doi:10.2174/1381612053507648

Cited by 111 publications

(72 citation statements)

References 195 publications

(200 reference statements)

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“…The balance between apoptosis and necrosis after PDT in vitro depends on several parameters, including the total PDT dose (PDT dose is the product of PS concentration and light fluence), the intracellular localization of the PS, the fluence rate, the oxygen concentration and the cell type 4 . There is an extensive body of literature that examines the pathways of apoptosis that are induced after PDT in both normal and tumour cells in tissue culture, such as signalling pathways 30,31 , mitochondrial events 4 and mediators of apoptosis 32 . The occurrence of apoptosis after PDT in tumours in vivo has also been shown [33][34][35] , but there have been no studies looking at in vivo clearance mechanisms of apoptotic cells in tumours after PDT.…”

Section: Effects Of Pdt On Tumour Cellsmentioning

confidence: 99%

Photodynamic therapy and anti-tumour immunity

2006

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Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells.The principle of photodynamic therapy (PDT) was first proposed over 100 years ago 1 . A recent review in Nature Reviews Cancer by Rakesh Jain and colleagues described some of the historical milestones in the development of PDT as a cancer treatment2. Many of the photosensitizers (PSs) that have been studied since PDT was first proposed are based on a porphyrin-like nucleus 3 . PSs function as catalysts when they absorb visible light and then convert molecular oxygen to a range of highly reactive oxygen species (ROS). The ROS that are produced during PDT have been shown to destroy tumours by multifactorial mechanisms4 , 5 (FIG. 1). PDT has a direct affect on cancer cells, producing cell death by necrosis and/or apoptosis 6 . PDT also has an affect on the tumour vasculature, whereby illumination and ROS production causes the shutdown of vessels and subsequently deprives the tumour of oxygen and nutrients 7,8 . Finally, PDT also has a significant effect on the immune system 9-11 , which can be either immunostimulatory or immunosuppressive.Most of the commonly used cancer therapies are immunosuppressive. Chemotherapy and ionizing radiation delivered at doses sufficient to destroy tumours are known to be toxic to the bone marrow, which is the source of all cells of the immune system, and neutropaenia and other forms of myelosuppression are often the dose-limiting toxicity of these therapies. However, it should be noted that low doses of either ionizing radiation12 , 13 or chemotherapy14 can have immunostimulatory effects, including the induction of heat-shock © 2006 Nature Publishing Group Correspondence to M.R.H. Hamblin@helix.mgh.harvard.edu. Competing interests statementThe authors declare no competing financial interests. DATABASES NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2010 September 6. Published in final edited form as:Nat Rev Cancer. 2006 July ; 6(7): 535-545. doi:10.1038/nrc1894. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript proteins 15 . Less well known is the fact that major surgery can also have an immunosuppressive effect that leads to a significant diminution of lymphocyte and natural killer (NK) cell function 16 . The ideal cancer therapy would not only destroy the primary tumour, but at the same time trigger the immune system to recognize, track down and destroy any remaining tumour cells, be they at or near the site of the primary tumour or distant microm...

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Section: Effects Of Pdt On Tumour Cellsmentioning

confidence: 99%

Photodynamic therapy and anti-tumour immunity

2006

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“…After 4 and 12 h, PSs were localised in the plasma membrane and in peripheral regions of the cytoplasm, and more necrotic cells in comparison to apoptotic were observed after longer time periods, and especially when a higher light dose was used (Kramer-Marek et al 2006). Conversely, targeting mitochondria in PDT is preferable to targeting plasma membrane and lysosomes, because it was shown to induce apoptosis rapidly, both in vivo and in vitro (Morgan and Oseroff 2001;Almeida et al 2004;Plaetzer et al 2005;Bonneau and Vever-Bizet 2008).…”

Section: Lipophilicity and Cellular Uptakementioning

confidence: 99%

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

2017

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Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targeting, localised action and stimulation of the immune responses. Further improvements and broader use of PDT could be accomplished by designing new photosensitisers with increased selectivity and bioavailability. Porphyrin-based photosensitisers with amphiphilic properties, bearing one or more positive charges, are an effective tool in PDT against cancers, microbial infections and, most recently, autoimmune skin disorders. The aim of the review is to present some of the recent examples of the applications and research that employ this specific group of photosensitisers. Furthermore, we will highlight the link between their structural characteristics and PDT efficiency, which will be helpful as guidelines for rational design and evaluation of new PSs.

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“…PDT causes tumour damage directly by inducing necrosis, apoptosis (Dougherty et al 1998, Kessel & Luo 1998, Plaetzer et al 2005 or autophagy (Kessel et al 2006, Buytaert et al 2006 in the tumour cells. PDT may also stiumulate shutdown of the tumour vasculature (Fingar et al 1999, Engbrecht et al 1999, Chen et al 2002, Woodhams et al 2006 and, in addition, PDT is shown preclinically to activate antitumour immunity (Castano et al 2006, Kousis et al 2007.…”

Section: Pdt Mediated Targeting Of Tumoursmentioning

confidence: 99%