# Photodynamic Therapy Effects on Oral Dysplastic Keratinocyte Cell Cultures: A Systematic Review
## 1 Introduction  
Typical photodynamic therapy (PDT) is a non-invasive approach involving a photosensitizer, light source, and oxygen to selectively produce a cytotoxic effect on targeted tissue [1]. The several combinations of a light source and photosensitizer allow this technique to target different lesions [2]. The molecular mechanism of PDT is based on three elements: the photosensitizer (PS); light with the appropriate wavelength; and dissolved oxygen in the cells [3]. These three compounds create the desired results within pathological tissues through mutual interactions. Photosensitizer molecules absorb light of the proper wavelength, starting the activation processes that leads to the death of selected cells [4]. The main photosensitizers studied in oral medicine are 5-aminolevulinic acid(5-ALA), methylene blue, and toluidine blue, and the wavelength of the light source can vary from 600 to 800 nm [5; 6]. PDT has been used in diverse specialties from ophthalmology to gynecology, including diagnostics and numerous dental domains such as endodontics, restorative dentistry, periodonontology, and oral medicine [7; 8; 9; 10; 11; 12]. In this field, PDT has been increasingly studied for its potential role in the treatment of oral potentially malignant disorders (OPMDs) such as oral leukoplakia (OL) and oral lichen planus (OLP) [13; 14; 15]. OPMDs are disorders with a high risk of progression to oral squamous cell carcinoma (OSCC). During the 2005 World Health Organisation (WHO) workshop, the terminology, definitions, and classification of oral lesions with a predisposition to malignant transformation were discussed. The term \"potentially malignant disorders\" was suggested. OPMDs include a group of conditions involving the oral mucosa with a raised risk of malignancy and comprised oral leukoplakia, erythrolpakia, erythrolekoplakia, and proliferative verrucous leukoplakia (PVL). Although malignant degeneration is the most feared and meaningful outcome, fortunately, not all lesions progress to that stage. They may last unchanged, broaden or reduce in size, or resolve completely. Presently, the degree of oral epithelial dysplasia (OED) is directly related to malignant transformation. Most authors agree that the risk of progression rises with the degree of OED. Indeed, most literature corroborates that OED has a significant risk of malignant transformation and should be considered in the clinical risk management process of OPMD progression [3; 16; 17]. The in vitro models provide a controlled environment for evaluating the phototoxicity of PDT agents, light sources, and treatment conditions. PDT has shown a cytotoxic effect due to the production of reactive oxygen species (ROS), microvascular alteration, and the activation of the immune system [18]. In vitro PDT also allows for the study of the molecular changes that occur in response to PDT, providing valuable proof to assess the treatment's biological effects [19]. The ability of PDT to selectively target lesional tissue allows the clinician to improve the prognosis of patients with OPMDs significantly [20]. Moreover, in vitro PDT can provide valuable information on the optimal treatment parameters, including photosensizer concentration, light dose, and treatment time, which can be used to optimize in vivo PDT treatments [21]. However, there is still much to be learned about the mechanisms and limitations of in vitro PDT, and continued research in this area is crucial to realize the full potential of PDT for the treatment of OPMDs and other oral diseases. Cell culture models provide a controlled environment for evaluating the phototoxicity of PDT agents, light sources, and treatment conditions, and they allow for the exploration of the molecular changes that happen in response to PDT [22]. In vitro, PDT also provides valuable information on the optimal treatment parameters, including photosensitizer concentration, light dose, and treatment time, which can be used to optimize in vivo PDT treatments.