Perspectives of photodynamic therapy in biotechnology

Highlights

• Photodynamic therapy moves through the most diverse areas of biotechnology;

• Results in clinical practice show that PDT is interesting for biotechnology;

• PDT avoids resistance to photosensitizers, contrary to what occurs in chemotherapy;

• Challenges of the PDT are the development of effective and non-toxic photosensitizers for humans;

• PDT shows a steady growth in agriculture.

Abstract

Photodynamic therapy (PDT) is a current and innovative technique that can be applied in different areas, such as medical, biotechnological, veterinary, among others, both for the treatment of different pathologies, as well as for diagnosis. It is based on the action of light to activate photosensitizers that will perform their activity on target tissues, presenting high sensitivity and less adverse effects. Therefore, knowing that biotechnology aims to use processes to develop products aimed at improving the quality of life of human and the environment, and optimizing therapeutic actions, researchers have been used PDT as a tool of choice. This review aims to identify the impacts and perspectives and challenges of PDT in different areas of biotechnology, such as health and agriculture and oncology. Our search demonstrated that PDT has an important impact around  oncology, minimizing the adverse effects and resistance to chemotherapeutic to the current treatments available for cancer. Veterinary medicine is another area with continuous interest in this therapy, since studies have shown promising results for the treatment of different animal pathologies such as Bovine mastitis, Malassezia, cutaneous hemangiosarcoma, among others. In agriculture, PDT has been used, for example, to remove traces of antibiotics of milk. The challenges, in general, of PDT in the field of biotechnology are mainly the development of effective and non-toxic or less toxic photosensitizers for humans, animals and plants. We believe that there is a current and future potential for PDT in different fields of biotechnology due to the existing demand.

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.