Editorial [ Hot Topic: Applications of the Photodynamic Therapy to Cancer,Water- and Vector-Borne Diseases (Guest Editor: Luigi E. Xodo )]

Applications of the Photodynamic Therapy to Cancer, Water- and Vector-Borne Diseases Photodynamic therapy (PDT) is a clinically approved treatment modality for various types of diseases, including cancer, that produces a selective cytotoxic effect on the target cells. It involves the use of a photosensitizing molecule and a source of light with a wavelength that corresponds to the absorption band of the photosensitizer. After photoactivation, the photosensitizer occupies an excited triplet state from which it transfers its energy to neighboring oxygen molecules, thus generating singlet oxygen and reactive oxygen species (\u201coxidative stress\u201d) which lead to cell death mediated by apoptosis and/or necrosis. PDT is less invasive than conventional chemotherapy, as the photosensitizer is not cytotoxic in the dark and the photoprocess is confined to the diseased tissue irradiated by light. In addition to the treatment of cancer and precancerous conditions, the use of PDT to cure microbial localized infections and inactivate pathogens is rapidly expanding. This special issue will address (i) the application of nanotechnology to PDT for improving the delivery of photosensitizers to the diseased tissue; (ii) the molecular response of cancer cells to the naturally-occurring photosensitizer hypericin; (iii) the photosensitizing properties of pheophorbide, a chlorophyll derivative, as a free or conjugated molecule; (iv) applications of PDT to water- and vector-borne diseases. Most of the clinically used photosensitizers are scarcely soluble in aqueous media, they do not accumulate efficiently in tumor tissues and often show an undesired liver accumulation. In an effort to overcome these shortcomings, research work has recently been directed to the development of nanoparticle-based photosensitizers. The contribution of Frochot and co-workers summarizes the use of nanoparticles (NPs) to enhance the delivery of scarcely soluble photosensitizers. NP technology offers a variety of advantages that are discussed in this review, including the transport of hydrophobic drugs in the blood, the possibility to decorate the NP surface with specific molecules in order to improve both uptake and tumor selectivity, the capacity of NPs to deliver a high \u201cpayload\u201d in the diseased tissue and, in certain cases, the possibility to excite directly NPs to generate oxidative stress. The review describes the chemical nature of NPs and the recent advances in the area of non-polymeric nanoparticles. A comprehensive presentation of gold and silica nanoparticles, carbon nanotubes, TiO2/ZnO and magnetic nanoparticles is provided. Krammer and Verwanger focus their review on the molecular response of cancer cells to PDT. The authors provide a thorough analysis of the cellular response to hypericin-induced photodamage and describe how the hypericin-PDT dose can dictate cell growth or cell death. Low doses stimulate cell growth via the p38 or JNK survival pathways, whereas high doses favor apoptosis or autophagic cell death, depending on the availability of Bax/Bak. The different modes of cellular responses correlate with the PDT-protocol, photosensitizer localization, cell damage protection and available intracellular energy. This review provides useful information for the design of new protocols aiming to reduce cell recurrence in PDT. Xodo and coworkers provide an update of the studies carried out with pheophorbide a (Pba), a derivative of chlorophyll a which shows a high PDT potential but has not yet been used in clinic. Their review refers to the basic reports describing the photophysical properties of Pba, its capacity to induce apoptosis in cancer cells, its pharmacokinetics and its in vivo efficacy against primary tumor growth. The authors discuss the efficiency in vivo of Pba conjugated to carrier polymers such as polyethylene glycol or peptide molecules. They also report that Pba is a generator of nitric oxide (NO) and that low intracellular NO levels (low dose Pba-PDT) seem to be responsible for cell recurrence through activation of NF-kB/anti-apoptotic Snail and repression of pro-apoptotic RKIP. In contrast, high NO levels (high dose Pba-PDT) repress NF-kB/Snail and activate pro-apoptotic RKIP. Finally, the review discusses the correlation between PDT and the NF-kB/Snail/RPIK loop, in the perspective of developing novel strategies to reduce cellular rescue in tissue regions which receive a low dose PDT. The last review, by Coppellotti and co-workers, reports on porphyrin/phthalocyanines/chlorines photosensitized processes in the prevention and treatment of water- and vector-borne diseases. The spreading of epidemic diseases due to the diffusion of antibiotic-resistant microbial strains makes PDT an attractive alternative to most of the presently employed therapeutic modalities. The field of antimicrobial PDT is rapidly growing, as suggested by the identification of novel photosensitizing agents with a high selectivity for microbial cell targeting. The application of PDT to water disinfection appears particularly attractive, as it can be achieved by the concerted action of sunlight and photosensitizers of natural origin that guarantee a minimal impact on the environment. The review outlines the principal antimicrobial photodynamic approaches which have been so far proposed to inactivate a large variety of pathogens causing water-borne diseases (bacteria, protozoa, fungi and metazoa) and the vectors (protozoa and arthropods) responsible for vector\u2013borne diseases. I hope this special issue will be beneficial to researchers working in the field of photodynamic therapy. It is important to acknowledge that this issue focuses on only a small part of what is known about PDT. More exhaustive reviews on PDT have been published in the last few years