Peripheral neural cell sensitivity to mTHPC-mediated photodynamic therapy in a 3D in vitro model

Abstract

BACKGROUND: The effect of photodynamic therapy (PDT) on neural cells is important when tumours are within or adjacent to the nervous system. The purpose of this study was to investigate PDT using the photosensitiser, meta-tetrahydroxyphenyl chlorin (mTHPC), on rat neurons and satellite glia, compared with human adenocarcinoma cells (MCF-7). METHODS: Fluorescence microscopy confirmed that mTHPC was incorporated into all three cell types. Sensitivity of cells exposed to mTHPC-PDT (0 -10 mg ml -1 ) was determined in a novel 3-dimensional collagen gel culture system. Cell death was quantified using propidium iodide and cell types were distinguished using immunocytochemistry. In some cases, neuron survival was confirmed by measuring subsequent neurite growth in monolayer culture. RESULTS: MCF-7s and satellite glia were significantly more sensitive to PDT than neurons. Importantly, 4 mg ml -1 mTHPC-PDT caused no significant neuron death compared with untreated controls but was sufficient to elicit substantial cell death in the other cell types. Initially, treatment reduced neurite length; neurons then extended neurites equivalent to those of untreated controls. The protocol was validated using hypericin (0 -3 mg ml -1 ), which caused neuron death equivalent to other cell types. CONCLUSION: Neurons in culture can survive mTHPC-PDT under conditions sufficient to kill tumour cells and other nervous system cells.

Photodynamic suppression of Enterococcus faecalis using the photosensitizer mTHPC

“…In the case of mTHPC, the potential dark toxic effect is examined for several cell types. Depending on PS concentration, dark incubation time, cell line and drug formulation, the dark toxicity of mTHPC is rated to be low 56–59. Furthermore, it is shown that aPDT is a save procedure for normal adjacent cells of the apical region.…”

Bipolar tetraether lipids derived from thermoacidophilic archaeon Sulfolobus acidocaldarius for membrane stabilization of chlorin e6 based liposomes for photodynamic therapy

“…The time interval between Ce6 administration and light delivery was 3 h. Consequently, complete medium was exchanged and light triggered effect was performed using UVA at 320-400 basically as previously described [30,31]using long-wave UVA light (CAMAG, Germany) at k ex = 366 -nm with 2.2 mW/cm 2 providing an energy equivalent to 2.6 J/cm 2 . The irradiation was continuously performed for 20 min, and cells were incubated for 24 h [32]. Cytotoxicity was determined by measurement of cell viability as a function of cellular redox potential as previously reported [33].…”

Photodynamic therapy in the upper aerodigestive tract. Overview and outlook

“…Until recently tumor invasion to the carotid artery has been a contraindication to PDT but more recently prophylactic endoluminal carotid stenting has been suggested and might overcome some of these problems . Another big advantage is the apparent lack of nerve damage. While PDT causes cellular death in many cell types, it does not seem to do so in neurons . This is especially important in the head and neck area, where nerve preservation is crucial for function preservation and where the “gold standard treatment” of head and neck cancer often goes along with ablative and reconstructive surgery and chemoradiotherapy. There is usually no drug toxicity, except photosensitivity.…”