Invited ReviewPerspectives of photodynamic therapy in biotechnology
Introduction
Photodynamic therapy (PDT) has been an interesting ally in different areas of knowledge. Its mechanism of action is based on the application of photosensitizers activated locally or systemically by light with an oxygen source, at an appropriate wavelength, and from this application occurs the generation of reactive oxygen species (ROS - singlet oxygen and radical species), responsible for triggering the expected results [1]. Studies in the field of human and animal health, especially dermatology, oncology, urology, microbiology, parasitology [[2], [3], [4]] and agriculture [5,6] has been demonstrating how eclectic and interesting this therapy can be (Fig. 1).
In this sense, biotechnology that aims to use cellular and biomolecular processes to develop technologies and products, aiming to improve life and health on the planet, has a total interest in developing products that may use tools that can be more effective and less aggressive either to humans, animals and plants [7]. For this reason, PDT has been widely used in the field of biotechnological treatments for the most different pathologies, such as method of choice for treatment of age-related macular degeneration and is appreciated as minimally invasive therapeutic procedure to treat skin, esophageal, head and neck, lung, and bladder cancers with high cure rates, low side effects, and excellent cosmetic outcome [8].
Still, in this context, it would be very interesting to think of molecules that could be marked and activated by light directly on the tissue of interest, for diagnostic purposes, for example, tetrapyrrole macrocycles (Fig. 2) [2,9]. Fig. 2A highlights some molecules with their effectiveness highlighted, for example, the mixture of oligomers Photofrin®, which is a photosensitizer used in photodynamic therapy and radiotherapy and for the treatment of lung carcinoma and esophageal cancer [10]. Foscan®, a drug-based on a tetra-(3-hydroxyphenyl)chlorin (temoporfin), is a photosensitizer commercialized in Europe and widely used in photodynamic therapy for the treatment of head and neck carcinoma [11]. Other chlorophyll derivatives, such as Chlorin e6, Visudyne® and Tookad®, are also used in the treatment of cancer by photodynamic action [12,13]. A new generation of photosensitizers for application in PDT has also shown success in this area (Fig. 2B), as is the case with Redaporfin®, a third-generation bacteriochlorin derivative used in the treatment of cancer and produced by Luzitin SA (Coimbra - Portugal) [14] and the Lutex® derivative (Lutrin/Antrin) based on a lutetium texafirin structure (Texas-shaped porphyrin) that exhibited an excellent response in preclinical breast cancer studies and prostate [15,16].
In this context, we could also think of molecules that could not only diagnose but also treat the patient simultaneously. We are at the frontier of knowledge and the development of such forms of treatment/diagnosis [17].
Another area that has shown interest in PDT is that of bioprospecting, after all, have as precept is the systematic search for organisms, genes, enzymes, compounds, processes and parts from living beings that have economic potential and lead to the development of a product [18]. We know that one of the greatest difficulties in the management of photosensitizers is linked to the fact of low solubility in water, the most appropriate vehicle for future formulations [19]. Thus, due to this high hydrophobicity, encapsulation approaches have been considered to minimize the formation of inactive aggregates in an aqueous environment. [20].
The vast majority of controlled delivery systems are based on nanoparticles (NP) or other nanostructures [21]. NPs, which usually range in size from 1 to 100 nm, reveal unique physical and chemical properties and are being explored for photosensitizers in order to optimize current treatment regimes in PDT [22]. Still, it is important to mention that in addition to the NPs (most commonly used) the encapsulation of the photosensitizer can occur through a system of micelles, liposomes, biodegradable NPs, conjugating the photosensitizer with hydrophobic polymers such as polyethylene glycol (PEG) [19].
These modifications end up bioprospect old and new photosensitizers which end up optimizing their specificity, selectivity, increasing their action time, leading to a better biological response.
Thus, the areas of biotechnology and bioprospecting are closely related, showing a special interest in photodynamic processes, due to the advantages it presents. Thus, this perspective aimed to assess the impact of PDT on biotechnology, the main goals and challenges within this field in the current scenario.
Section snippets
Impacts of Photodynamic therapy at Biotechnology
In this session we will address the impacts that the PDT has on the different areas of knowledge of biotechnology. We chose to cover the areas of human and veterinary health and agriculture. We also added a topic specifically involving cancer, as it is the area of study of our research group.
Challenges and Perspectives of Photodynamic Therapy in Biotechnology
The challenges of PDT in the field of biotechnology are the development of effective and non-toxic or less toxic photosensitizers for humans, animals and plants. The focus should be on third generation molecules, which include the characteristics necessary for the functioning of the PDT, with increased and selectivity in the generation of reactive oxygen species and efficiency.
Results in clinical practice demonstrate how interesting the therapy is, including financially for biotechnology. One
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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