**5. Future perspectives**

Photodynamic Therapy has been used in clinical applications with significant success. Several studies have focused on the suitable conditions to improve the clinical results, such as the optimization of the incident light intensity. Indeed, the importance of irradiance is a determinant of PDT-induced pain. The increased use of low irradiance PDT may have a considerable impact on pain, which currently is the main limiting factor to successful delivery of PDT in some patients [186].

Another area of improvement of the PDT application is focused on the increase of the aqueous solubility of the photosensitizers. In fact, the photosensitizers require being suitable to several types of administration in biological medium. In this context, interesting photosensitizers that present low water solubility, such as C60, constitute an area of scientific efforts. C60 can be accumulated selectively in the target point. However, the biological application of C60 is limited due to its poor solubility in water [187]. To improve the solubility of C60 in water, several water-soluble derivatives have been synthesized. Furthermore, other solubilization methods for C60 have been explored using cyclodextins, calixerenes, micelles, liposomes, and poly(N-vinyl-2-pyrroridone) (PNVP). In general, coreshell polymer micelles can be formed spontaneously by amphiphilic diblock copolymers due to association between hydrophobic blocks in water. The hydrophobic drugs can be incorporated into the hydrophobic core of the polymer micelle, and thus, the drugs can be solubilized in water. Nanosized water-soluble core-shell type polymer micelles can allow long circulation in the blood stream avoiding reticuloendothelial systems (RESs) and can be utilized for their enhanced permeability and retention (EPR) effect at solid tumor sites.

The production of ROS can be affected by factor, such as the aggregation and photobleaching of the photosensitizer. In fact, photosensitizers such as, for example, magnesium protoporphyrin (MgPpIX), have demonstrated that the aggregation and photobleaching reduce the photodynamic efficiency [188].

408 Advanced Aspects of Spectroscopy

ultra-cold atoms [181].

**5. Future perspectives** 

delivery of PDT in some patients [186].

The quantum behavior of extended aggregates of atomic and molecular monomers, containing from a just a few up to thousands of subunits, is attracting increasing attention in chemistry and physics, being that proeminent examples are aggregates of large dye molecules, chromophore assemblies describing the photosynthetic unit of assemblies of

According to their structure, dyes, such as phenotiazinium, exhibit J- or H-aggregates, which present very typical J- or H-absorption bands [182]. The aggregate absorption band is red-shifted in relation to the monomer absorption. These are the J-aggregates showing a very narrow band whose position is well-predicted by a theory ignoring intramolecular vibrations. By contrast, other dyes showed a shift towards the blue (i.e. higher absorption energies) and were termed H-aggregates (hypsochromic shift). Unlike the J-band, the line shape of the H-band generally shows a rich vibrational structure and has a width of the order of the monomeric band [183]. The J-band is polarized parallel to the rods, while the H-

Self-organized J-aggregates of dye molecules, known for over 60 years, are emerging as remarkably versatile quantum systems with applications in photography, opto-electronics,

Photodynamic Therapy has been used in clinical applications with significant success. Several studies have focused on the suitable conditions to improve the clinical results, such as the optimization of the incident light intensity. Indeed, the importance of irradiance is a determinant of PDT-induced pain. The increased use of low irradiance PDT may have a considerable impact on pain, which currently is the main limiting factor to successful

Another area of improvement of the PDT application is focused on the increase of the aqueous solubility of the photosensitizers. In fact, the photosensitizers require being suitable to several types of administration in biological medium. In this context, interesting photosensitizers that present low water solubility, such as C60, constitute an area of scientific efforts. C60 can be accumulated selectively in the target point. However, the biological application of C60 is limited due to its poor solubility in water [187]. To improve the solubility of C60 in water, several water-soluble derivatives have been synthesized. Furthermore, other solubilization methods for C60 have been explored using cyclodextins, calixerenes, micelles, liposomes, and poly(N-vinyl-2-pyrroridone) (PNVP). In general, coreshell polymer micelles can be formed spontaneously by amphiphilic diblock copolymers due to association between hydrophobic blocks in water. The hydrophobic drugs can be incorporated into the hydrophobic core of the polymer micelle, and thus, the drugs can be solubilized in water. Nanosized water-soluble core-shell type polymer micelles can allow long circulation in the blood stream avoiding reticuloendothelial systems (RESs) and can be utilized for their enhanced permeability and retention (EPR) effect at solid tumor sites.

band is polarized perpendicularly to the rod long-axis [184].

solar cells, photobiology and as supramolecular fibres [185].

Low-level laser therapy has been used to speed up healing process of pressure ulcers due to its antiinflammatory, analgesic, anti-edematous, and scarring effects, since there is no consensus on its effect on infected ulcers [189]. It is an interesting topic to be evaluated in novel studies.

It is known that Gram positive bacteria are more sensitive to PDT as compared to Gram negative species. However, the use of cationic photosensitizers or agents that increase the permeability of the outer membrane allows the effective killing of Gram negative organisms [190]. Some photosensitizers have an innate positive charge, but some approaches are focused on to link photosensitizers to a cationic molecular vehicle, such as poly-L-lysine [190].

Photodynamic therapy has been also applied in dentistry, in endodontic treatments, with auspicious results regarding the control of microbial infections associated to this type of odontologic therapy [191].

The increasing application of PDT has motivated the development of other therapeutic techniques, with similar principles. We can mention the case of Sonodynamic Therapy (SDT). In 1989, Umemura and co-workers first pioneered the development of non-thermal ultrasound activating a group of photosensitizers for treating tumor, which is called Sonodynamic Therapy (SDT) [192]. They reported that the photosensitive compounds activated by ultrasound can kill cancerous cells and suppress the growth of tumor. Otherwise, they also thought highly of that the ultrasound could reach deep-seated tumor and maintain the focus energy in a small volume because of exceedingly strong penetration ability and mature focusing technology [193]. Particularly, SDT was developed from the wellknown PDT but only put up low phototoxicity. Therefore, in recent years, along with the lucubration the SDT has attracted considerable attention and has been considered as a promising tumor treatment method [192].

Regarding the development of photosensitizers, it is important to register the relevant role of phthalocyanines. Phthalocyanines (Pcs) are highly delocalized p-conjugated organic systems and exhibit wide variety of roles in a various high technological areas such as semiconductor devices, liquid crystals, sensors, catalysts, non-linear optics, photovoltaic solar cells and PDT [194, 195]. They are among the most important promising chemical compounds by advantage of their stability, photophysical, photochemical, redox and coordination properties. The properties of Pcs depend on their molecular composition with the number; position and nature of substituents and type of central metal play an important role in controlling their properties [194].

Indeed, Pcs have many considerable physical and chemical features, which have motivated the interest of several investigators because of their physico-chemical properties [195]. The presence of different substituents on the Pc ring also leads to increased solubility and supramolecular organizations with improved physicochemical characteristics, depending of the interest in terms of application [194]. In fact, phthalocyanines are very versatile chemical systems, which allow great variability of adjustment of properties in the process of chemical synthesis. This great number of structural possibilities has been utilized in many fields, since the different phthalocyanines can be applied in quite different areas, such as gas sensors, semiconductor materials, photovoltaic cells, liquid crystals, optical limiting devices, molecular electronics, non-linear optical applications, Langmuir-Blodgett films, fibrous assemblies and PDT [195].
