3 Mechanism of PDT of porphyrin
The anti-tumor mechanism of PDT consists of two main phases (Fig. 5).
Photosensitizer (PS) accumulates at the tumor site after intravenous
injection and then irradiates the tumor tissue at a specific wavelength.
In the first stage, PS changes from the ground state (single-linear
state (S0)) to the excited single-linear state
(S1) after being irradiated (nanosecond range). The
excited state of the photosensitizer is very unstable and loses excess
energy through non-radiative (thermal emission) or radiative
(fluorescence emission) pathways(Bouramtane et al. 2019; Castano et al.
2005; Robertson et al. 2009). The excited single-linear state can
produce a more stable excited trilinear state (T1) with
parallel spins (microsecond to millisecond range) by inter-system
crossover. In the T1, PS can undergo two types of
reactions (Type I reactions and Type II reactions). In the first type of
pathway, electron or hydrogen atom transfer occurs between the
T1 photosensitizer and the cell membrane of the
biomolecule(Z. 2003). This process forms free radicals and radical ions,
leading to the production of cytotoxic hydroxyl radicals (•OH), hydrogen
peroxide (H2O2), and other ROS. The
second type of reaction involves the interaction between electronically
excited trilinear state photosensitizers and the ground state trilinear
state molecular oxygen (3O2). The
excited PS transfers energy to 3O2 to
form the singlet oxygen. The product1O2 can react with a variety of
biomolecules and is a key factor in the induction of apoptosis and
tissue destruction in cancer cells(Buytaert et al. 2007; Kessel and
Oleinick 2010; Mehraban and Freeman 2015). In addition, it has been
demonstrated that type I and type II reactions can occur simultaneously
and independently, and that type II reactions play a more important role
in PDT(Castano et al. 2004; Ethirajan et al. 2011; Gomes et al. 2018;
Lin et al. 2020).