The effects of protoporphyrin IX-induced photodynamic therapy with and without iron chelation on human squamous carcinoma cells cultured under normoxic, hypoxic and hyperoxic conditions

Blake, Emma; Allen, James H.; Curnow, Alison

doi:10.1016/j.pdpdt.2013.06.006

Cited by 14 publications

(12 citation statements)

References 29 publications

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“…Blake, Allen and Curnow [38] in the UK studied the effect of iron chelation and oxygen concentration on the accumulation, photobleaching and cytotoxicity of protoporphyrin IX (PpIX) during PDT of human glioma cells in vitro. They tested three PpIX precursors, aminolevulinic acid (ALA) and its esters, methyl aminolevulinate (MAL) and hexyl aminolevulinate (HAL), with an iron chelator CP94.…”

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confidence: 99%

Photodynamic Therapy as an Emerging Treatment Modality for Cancer and Non-Cancer Diseases

Hu¹

2014

J Anal Bioanal Tech

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Hu et al., J Anal Bioanal Tech 2014, S1 http://dx.doi.org/10.4172/2155-9872.S1-e001 ISSN: 2155-9872 JABT, an open access journal Photodynamic Therapy-Cancer J Anal Bioanal TechPhotodynamic therapy (PDT) is a treatment modality involving photoactivatable chemicals (called photosensitizers), light and tissue oxygen [1][2][3][4][5][6]. PDT has clinical applications in the treatment of a variety of solid cancers [4,7-21], including but not limited to those of lung, skin, breast, head and neck, digestive tract, pancreas, liver, bladder, ovary, prostate and brain. In addition, there are many clinical applications of PDT for treatment of a wide range of non-cancerous conditions, such as bacterial and fungal infections; hyperproliferative or inflammatory conditions, such as macular degeneration or psoriasis; and premalignant conditions, such as actinic keratosis [22] and Barrett's esophagus [23]. To achieve better therapeutic efficacy, new photosensitizers and novel light sources are continuously being developed, and the mechanisms of action are becoming better understood [24,25]. To achieve improved tumor selectivity and to reduce side effects in the treatment of cancer, the concept of targeted photodynamic therapy has been successfully developed by attaching specific functionalities to the photosensitizer, such as antibodies recognizing tumor antigens [26,27], or ligands and peptides to recognize receptors [28], which could be selectively expressed on one of the two major tumor compartments, either on the malignant cells or on tumor neovasculature. To achieve better efficacy than PDT that is targeted to a single tumor compartment (stPDT), a recent editorial [29] in this Journal summarized a new PDT approach (Figure 1), which was designed for dual targeting of photosensitizers (dtPDT) to both malignant cells and neovasculature [30,31] by conjugating photosensitizers to a protein, factor VII, the natural ligand for tissue factor. This approach allows for dual targeting of malignant cells and of tumor neovasculature, both of which either overexpress or selectively express tissue factor [30][31][32][33], respectively.In this special issue on PDT-Cancer, PDT scientists and experts worldwide contributed seven peer-reviewed articles. These review and research articles broadly cover the use and applications of PDT for cancer, for infections and for inflammatory conditions. Menon and Stafinski [34] in Canada thoroughly reviewed reports of clinical applications and clinical trials of PDT for the treatment of different types of cancers that were published in English between January 1997 and June 2011. They summarized a total of 266 studies, which involved 11,427 patients and 34 different types of cancer in diverse organs, such as anal and perianal cutaneous cancers, as well as cancers of the bile duct, bladder, brain, breast, cervical, esophageal, eye, gastrointestinal, head and neck, lung, peritoneal cavity, colorectal, liver, ovary, pancreas, prostate, skin, vulva, etc. Tsipursky, Churgin, Conway and Peyman [35] in the Uni...

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confidence: 99%

Photodynamic Therapy as an Emerging Treatment Modality for Cancer and Non-Cancer Diseases

Hu¹

2014

J Anal Bioanal Tech

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“…Furthermore, additional studies undertaken with CP94 alone within A431 cells have indicated that significantly increased PpIX levels and subsequent cytotoxicity can be produced 13 when using HAL (the hexyl ester of ALA) as well as ALA or MAL as the PpIX precursor, when PDT is conducted within a variety of different oxygen conditions [31]. This experimentation has been extended here to consider the effect of topical CP94 administration in vivo in a normal rat skin model.…”

Section: Discussionmentioning

confidence: 96%

“…This experimentation has been extended here to consider the effect of topical CP94 administration in vivo in a normal rat skin model. In light of our previous findings with CP94 augmentation of PpIX-PDT demonstrated in epidermal squamous carcinoma cells (A431) [30][31], a colonic tumour model [33] and dermatological skin lesions [35][36], it was not deemed necessary to create a neoplastic skin model here when our main focus was to assess PpIX production/excised tissue fluorescence (which we have been unable to do clinically due to ethical constraints).…”

Section: Discussionmentioning

confidence: 99%

“…Additional in vitro investigation has indicated that this effect can also be elucidated when using HAL (the hexyl ester of ALA) as well as ALA or MAL as the PpIX precursor [31]. In vivo, CP94 has been utilised intravenously to enhance ALAinduced PpIX fluorescence and necrosis in the normal rat colon [32] and to also produce greater tumour necrosis within a colonic rat tumour model [33].…”

Section: Introductionmentioning

confidence: 99%

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Enhancing Protoporphyrin IX induced Photodynamic Therapy with a Topical Iron Chelating Agent in a Normal Skin Model

Curnow¹,

Macrobert²

2016

J Heavy Met Toxicity Dis

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Protoporphyrin IX (PpIX)-induced photodynamic therapy (PDT) is being utilised within dermatological practice as a topical method of localised ablation of nonmelanoma skin cancer/precancer. Standardised protocols have been implemented to good effect when the disease remains superficial but improvement is required to widen the application of this light activated drug therapy to treat thicker or acrally located conditions. As innate haem biosynthesis is exploited to accumulate the light sensitive PpIX from a topically applied inert prodrug (aminolaevulinic acid; ALA), this pathway can be further manipulated through the concurrent administration of an iron chelating agent to hyper-accumulate PpIX by temporarily reducing its iron dependent conversion to haem.A topical preparation of ALA was applied to normal rat skin with or without the hydroxypyridinone iron chelator, CP94. Image analysis quantification of tissue fluorescence following excision indicated that ALA plus CP94 produced 29.0% more fluorescence than ALA alone (p < 0.09), peaking at 5 hours. Furthermore, fluorescence spectroscopy of frozen skin samples from each treatment group were characteristic of PpIX (maxima 636 +/-2 nm), indicating that topical CP94 administration elevated PpIX levels without significantly producing any other fluorescent species. When PDT efficacy was considered post irradiation, a substantial three-fold increase in effect was observed 4 days after treatment when the iron chelator CP94 was co-administered topically with the prodrug (p < 0.07).It has therefore been established that the hydroxypyridinone CP94, is topically active within normal rat skin, effectively chelating iron to elevate PpIX accumulation and thus improve PDT efficacy.4

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“…Moreover, iron chelators also have the ability to inhibit ferrochelatase activity. Employing iron chelators prevents the formation of heme, and as a result, more PPIX accumulates inside the cells [42]. Up to now, the following iron chelators including ethylenediaminetetraacetic acid (EDTA), desferrioxamine (DFO), 1,2-diethyl-3-hydroxypyridin-4-one hydrochloride (CP94), and dexrazoxane (ICRF-187) [43•] have all been proved to increase PPIX accumulation and photosensitization in PDT.…”

Section: Improvements In Cellular Ppix Synthesismentioning

confidence: 99%

Current Advances in 5-Aminolevulinic Acid Mediated Photodynamic Therapy

et al. 2016

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Kennedy and Pottier discovered that photodynamic therapy (PDT) could be carried out using a procedure consisting of topical application of the porphyrin-precursor, 5-aminolevulinic acid (ALA) to the skin, followed after some time by illumination with various light parameters in the 1980s. Since then, ALA-PDT has expanded enormously and now covers most aspects of dermatological disease. The purpose of this review is to discuss a range of ingenious strategies that investigators have devised for improving the overall outcome (higher efficiency and lower side effects) of ALA-PDT. The big advance of using ALA esters instead of the free acid to improve skin penetration was conceived in the 1990s. A variety of more recent innovative approaches can be divided into three broad groups: (a) those relying on improving delivery or penetration of ALA into the skin; (b) those relying on ways to increase the synthesis of protoporphyrin IX inside the skin; (c) those relying on modification of the illumination parameters. In the first group, we have improved delivery of ALA with penetration-enhancing chemicals, iontophoresis, intracutaneous injection, or fractionated laser. There is also a large group of nanotechnology-related approaches with ALA being delivered using liposomes/ethosomes, ALA dendrimers, niosomes, mesoporous silica nanoparticles, conjugated gold nanoparticles, polymer nanoparticles, fullerene nanoparticles, and carbon nanotubes. In the second group, we can find the use of cellular differentiating agents, the use of iron chelators, and the effect of increasing the temperature. In the third group, we find methods designed to reduce pain as well as improve efficiency including fractionated light, daylight PDT, and wearable light sources for ambulatory PDT. This active area of research is expected to continue to provide a range of intriguing possibilities.

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The effects of protoporphyrin IX-induced photodynamic therapy with and without iron chelation on human squamous carcinoma cells cultured under normoxic, hypoxic and hyperoxic conditions

Abstract: Summary Background

Cited by 14 publications

References 29 publications

Photodynamic Therapy as an Emerging Treatment Modality for Cancer and Non-Cancer Diseases

Photodynamic Therapy as an Emerging Treatment Modality for Cancer and Non-Cancer Diseases

Enhancing Protoporphyrin IX induced Photodynamic Therapy with a Topical Iron Chelating Agent in a Normal Skin Model

Current Advances in 5-Aminolevulinic Acid Mediated Photodynamic Therapy

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