Biomedical Engineering – From Theory to Applications

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356 Biomedical Engineering – From Theory to Applications sensitized solar cells, pigments, in electrocatalysis, as electrodes in fuel cells, and as chemical sensors, but these issues are not the subject of this paper. Therefore the present chapter will only address the medical applications of porphyrins and metalloporphyrins with a special emphasis on photodynamic therapy. Fig. 1. Applications of porphyrins and metalloporphyrins Fig. 2. Ascendant trend of publications on the topic of porphyrins involved in photodynamic therapy, as indexed by ISI Web of Knowledge
Trends in Interdisciplinary Studies Revealing Porphyrinic Compounds Multivalency Towards Biomedical Application We summarize herein basic concepts in the field, stressing out theoretical and technological limitations that currently restrict multidisciplinary research for improving /enlarging theoretical and technological approaches in PDT and PDD using porphyrins. Special emphasis will be given to the development of novel porphyrinic structures related or derived from already confirmed structures and to put them in connection with PDT and PDD applications, focusing on symmetrical vs. asymmetrical molecular structures and on classical vs. more recent synthetic methods. Dosimetry issues for controlling and characterizing related processes, interdisciplinary approaches (chemistry, physics, biochemistry and biomedicine) will be also highlighted. The major role played by porphyrinoid systems in biomedical applications is due to their photochemical (energy and exciton transfer), redox (electron transfer, catalysis) and coordination properties (metal and axial ligand binding) and their conformational flexibility (functional control) (Senge et al., 2010). The issue of PDT will be extensively adressed in the next section, while other medical applications, some of them very recent, will be described in section 4. 2. Photodynamic therapy - main medical application of porphyrins PDT typically combines a photosensitizer, molecular oxygen and light to destroy cancer cells and microorganisms by oxidative stress (Bonnett R., 2000). Briefly, PDT is based on the ability of photosensitisers, including porphyrins, to selectively accumulate and kill tumour cells (Dougherty, 1987) by singlet oxygen ( 1O2) (Berenbaum & Bonnett, 1990), upon guided light activation with a particular wavelength (usually via laser endoscopy). Reactive oxygen species (ROS) produced by phagocytes underly physiological defense mechanisms against microorganisms, which are highly controlled to destroy pathogens, whilst minimally affecting the surrounding healthy tissues (Witko-Sarsat et al., 2000). As reviewed by Manda et al. (2009) cancer cells show an intrinsic oxidative phenotype, which makes them more sensitive to the deleterious action of additional oxidative stress generated for therapeutical purposes either by radiotherapy, PDT or even chemotherapy. PDT has gained increasing attention in the past decade as a targeted and less invasive treatment regimen for a number of medical conditions, spanning from various types of cancers and dysplasias to neoangiogenesis, macular degeneration, as well as bacterial infections. The advantage is that PDT provides a localized action rather than a systemic one, when compared to other cancer therapies which are more harmful to the patient. PDT for cancer treatment has been extensively reviewed (Allison & Sibata, 2010; Capella M.A.M. & Capella L.S., 2003; Dickson, 2003; Dolmans, 2003; Dougherty, 1998; O’Connor et al., 2009; Vrouenraets, 2003; Wilson B.C., 2002). The huge effort in PDT development is highlighted by 1074 papers in the field reviewed in PubMed in the last 2 years, while 72 clinical trials in PDT were ongoing in March 2011 (http://clinicaltrials.gov). 2.1 Mechanism of action As summarized in Fig. 3, there are two recognized mechanisms of action for PDT. The first mechanism (type I) involves light induced excitation of the photosensitizer, promoting an electron to a higher energy state. At this point a variety of reactions can take place. For example, the photosensitizer in the excited state can act as a reducing agent in the reaction to create ROS. Conversely, the excited photosensitizer may act as an oxidizing agent by filling the hole vacated by the excited electron. The second mechanism (type II) also 357
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BIOMEDICAL ENGINEERING - FROM THEOR
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VI Contents Chapter 9 Targeted Magn
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X Preface stand-alone and readers c
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110 Method (Detection) Analyte Matr
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120 6. Conclusion Biomedical Engine
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150 5. Conclusions Biomedical Engin
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162 1 st phase : half year 4 2 nd p
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166 7. Innovative active training B
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172 12. Maturing projects’ story
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180 16. Acknowledgments Biomedical
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190 R* M M M M MR*M O O O O M O R*
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196 Fig. 9. Chemical structure of 5
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198 Relative Intensity (AU) Biomedi
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204 2. Preparation of IO nanopartic
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256 3. Deposition techniques Biomed
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300 2. Nanoparticles in biomedical
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