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Photodynamic therapy / Photoimmunotherapy

Photodynamic therapy (PDT) is a multicomponent anticancer treatment that involves the administration of a photosensitizing drug and its subsequent activation by light of the appropriate wavelength to generate cytotoxic reactive oxygen species. Due to the low penetration depth of the light in tissue, PDT was originally used for the treatment of superficially localized tumors. Because irradiation is limited to the tumor site, PDT is relatively selective compared with other conventional cancer treatments. Furthermore, PDT has been reported to have the ability to inhibit multidrug resistance.

Photosensitizers are generally classified as porphyrinoids or nonporphyrinoids. Porphyrin-derived photosensitizers represent the most important class of photosensitizers due to their high molar absorption coefficient in the long wavelength (600–800 nm), high quantum yield of singlet oxygen generation, chemical stability, and preferential localization within the tumor.

The poor light absorption properties and the low tissue penetration depth of the light below 700 nm have stimulated the development of a second generation of photosensitizers among them porphyrins, phthalocyanines, naphthalocyanines and chlorins. Further, the development of the two-photon PDT could increase the penetration depth in tissue compared to conventional PDT.

Then, the development of third generation photosensitizers was driven by the interest in increasing the specificity of photosensitizers and subsequent accumulation in cancerous tissues. The approach consists in conjugating the photosensitizer to monoclonal antibodies directed against tumor-associated antigens. This approach currently represents an active research area and refers to the photoimmunotherapy (PIT).

REFERENCES
J. Schmitt, V. Heitz, A. Sour, F. Bolze, H. Ftouni, J.-F. Nicoud, L. Flamigni and B. Ventura, Diketopyrrolopyrrole-Porphyrin Conjugates with High Two-Photon Absorption and Singlet Oxygen Generation for Two-Photon Photodyanmic Therapy, Angew. Chem. Int. Ed., 2015, 54, 169-173.
G. Garcia, F. Hammerer, F. Poyer, S. Achelle, M.-P. Teulade-Fichou, and F. Maillard, Carbohydrate-conjugated porphyrin dimers: Synthesis and photobiological evaluation for a potential application in one-photon and two-photon photodynamic therapy, Bioorg. Med. Chem., 2013, 21, 153–165.
L. B. Josefsen, and R. W. Boyle, Unique Diagnostic and Therapeutic Roles of Porphyrins and Phthalocyanines in Photodynamic Therapy, Imaging and Theranostics, Theranosctics, 2012, 2(9), 916–966.
M. Ethirajan, Y. Chen, P. Joshi and R. K. Pandey, The role of porphyrin chemistry in tumor imaging and photodynamic therapy, Chem. Soc. Rev., 2011, 40, 340–362.
Handbook of Porphyrin Science with Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medicine
, Phototherapy, Radioimmunotherapy and Imaging, K. M. Kadish, K. M. Smith, R. Guilard, World Scientific, Singapore, 2010, Vol. 4.

Antimicrobial photodynamic inactivation

Antimicrobial photodynamic inactivation (PDI) is a procedure which combines a photosensitizer, light and oxygen leading to the formation of reactive oxygen species that destroy the microorganisms among them bacteria (including drug-resistant strains), yeasts, viruses and protozoa. This innovative technique can help to address the increasing problem of conventional microbial associated therapies, which induce antibiotic resistance since no microbial resistance was observed using PDI. All studies show that microorganisms are not able to develop resistance.

Porphyrins and phthalocyanines demonstrated to have a relatively low toxicity and generate efficiently reactive oxygen species. Hence, this important class of photosensitizers were studied as novel agents against pathogenic microorganisms. Many of these derivatives were synthesized by modification of their peripheral substituents. As biomimetic models of heme, they are actively accumulated by bacteria and some of them occur to be very effective antimicrobial agent. The PDI opens up innovative possibilities in advanced sterilization technology development and represents a unique alternative to prevent the drug-resistance.

REFERENCES
J. Almeida, J. P. C. Tomé, M. G. P. M. S. Neves, A. C. Tomé, J. A. S. Cavaleiro, A. Cunha, L. Costa, M. A. F. Faustino and A. Almeida, Photodynamic inactivation of multidrug-resistant bacteria in hospital wastewaters: influence of residual antibiotics, Photochem. Photobiol. Sci., 2014, 13, 626-633.
S. Murphy, C. Saurel, A. Morrissey, J. Tobin, M. Oelgemöller, K. Nolan, Photocatalytic activity of a porphyrin/TiO2 composite in the degradation of pharmaceuticals, Applied Catalysis B: Environmental, 2012, 119–120, 156–165.
J.–W. Choi, S.–G. Chung, K.–Y. Cho, K.–Y. Baek, S.–W. Hong, D.–J. Kim, S.–H. Lee, Photocatalytic Degradation of Chlorophenol Compounds using Poly Aromatic Star Copolymer, Water Air Soil Pollut, 2012, 223, 1437–1441.
S.–L. Wang, Y.–Y. Fang, Y. Yang, J.–Z. Liu, A.–P. Deng, X.–R. Zhao and Y.–P. Huang, Catalysis of organic pollutant photodegradation by metal phthalocyanines immobilized on TiO2@SiO2, Chinese Sci Bull, 2011, Vol. 56, No.10, 969−976.