## 1 Introduction  
Apical periodontitis (AP) is an inflammatory disease of the periapical tissues, which develops as a host immune response to microbial infection inside the root canal system (RCS) [1]. AP is typically asymptomatic and diagnosed through radiographic examinations. Its etiology is associated with the commensal oral microbiota, which invades and multiplies in the RCS following pulp necrosis due to factors such as caries, tooth trauma, defective restorations, or unsuccessful endodontic procedures [2]. Necrotized root canals are quickly inhabited by diverse bacterial communities, which extend to the surrounding connective tissues via the apical foramen, leading to the development of a periapical lesion [3]. Endodontic therapy seeks to reduce the bacterial load to levels that permit the modeling and healing of the affected bone tissue. However, to date, it has not been possible to find a therapeutic combination that is effective in every case. Existing endodontic treatment methods have been inadequate in lowering endodontic pathogens below detectable levels. In fact, AP remains notably prevalent [4]. This shortfall is likely due, in part, to the complex anatomy of the RCS, which hinders the elimination of bacteria in areas that are difficult for antimicrobial agents to reach, such as apical deltas, accessory canals, isthmuses, and dentinal tubules [5]. Additionally, the effectiveness of sodium hypochlorite (NaOCI) (the irrigant of choice in conventional endodontic therapy) can be limited by factors such as its concentration, exposure time, and volume within the root canals [6]. Consequently, it is evident that more advanced disinfection techniques are necessary for the thorough eradication of endodontic microbial biofilms. In this context, antimicrobial photodynamic therapy (aPDT) has been suggested to complement conventional endodontic therapy, in order to combat a wide range of endodontic infectious diseases [7]. The inactivation of micro-organisms by aPDT is based on the use of a chromophore or photosensitizer (PS)--a harmless natural or synthetic chemical solution--which is activated by low doses of visible light in the presence of oxygen to cause targeted cellular damage. The photodynamic process begins when an electron in the PS is excited to a higher energy level, leading to the formation of an excited state. This state is transient, as the energy can be dissipated as fluorescence or transferred to nearby molecular oxygen through an inter-system crossing mechanism [8] (Figure 1A). When a PS is excited by an affine wavelength, it generates a cascade of photochemical reactions, causing the generation of reactive oxygen species (ROS), such as hydroxyl radicals, hydrogen peroxide, and superoxide (type 1 reaction) and singlet oxygen (\({}^{1}\)O\({}_{2}\)) molecule (type 2 reaction) (Figure 1B), which have toxic effects on bacteria and fungi [9]. The cytotoxic effects of aPDT are primarily due to the oxidative stress induced by light  
Figure 1: Schematic representation of mechanisms of antimicrobial photodynamic therapy: (**A**) When light is absorbed, the PS is activated, shifting from its ground state to an excited singlet state. This excited state may undergo inter-system crossing, where the spin quantum number changes, resulting in a lower-energy, longer-lasting triplet state. The triplet state can then react through one or both of the oxygen-dependent mechanisms, known as Type I and Type II photoprocesses; (**B**) in the type I pathway, electron transfer reactions occur from the triplet PS state, involving a substrate to form radical ions (free radicals), which can then interact with oxygen to generate cytotoxic species such as superoxide, hydroxyl radicals, and lipid radicals. In contrast, in the Type II pathway, energy transfer from the triplet PS state to ground-state molecular oxygen occurs, producing singlet oxygen which can oxidize biological molecules such as proteins, nucleic acids, and lipids, leading to cytotoxic outcomes.