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INNOSC Theranostics and
Pharmacological Sciences The biochemical and biophysical guide for photodynamic therapy

In 1948, Figge and Weiland conducted extensive research to nearby molecules that do not absorb light. This energy
on the possibility of using various porphyrin derivatives or electron transfer results in the production of highly
in photodynamic therapy (PDT) and diagnostics. They reactive molecules, enabling PDT to function through
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demonstrated the use of hematoporphyrin (HDP) as three primary mechanisms: Direct destruction of target
a tool for cancer detection. However, at that time, this cells, damage to blood vessels that lead to ischemia and
approach still carried the risk of toxic side effects. They tumor cell death, and activation of the immune response.
also assessed the effectiveness of other compounds, such as PSs enhance the activation of immune cells, such as
coproporphyrin, protoporphyrin, and zinc HDP. In 1955, neutrophils, macrophages, and lymphocytes, which, in
scientist Schwartz investigated the nature of HDP and turn, increase the secretion of interleukin (IL)-6, IL-10, and
found that it was a mixture of many different porphyrins, tumor necrosis factor (TNF), contributing to tumor cell
each with distinct properties. PDT gained further death. Cell death in PDT occurs through two mechanisms:
development when it was discovered that HDP derivatives necrosis and apoptosis. Necrosis refers to the local death
increased the fluorescence of tumors in patients. This of tissues, which triggers acute inflammation at the site
breakthrough was made by a team of doctors from the of injury. The byproducts of necrotic tissue breakdown
Mayo Clinic. In a review by Kessel D published in 2019, are toxic to the body. On the other hand, apoptosis is
the historical details of the 1972 first usage of fluorescent programmed cell death, controlled enzymatically, and
in biology were described. This study demonstrated the does not induce inflammation. PS is a molecule with
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ability to eliminate glioma cells in tumors in both animal electrons arranged in specific molecular orbitals. In its
models and established cell cultures. 1,2 ground state, PS contains electron pairs with opposite
spins in low-energy orbitals. When exposed to light of a
Soon after, this mechanism was extended to the specific wavelength, PS absorbs energy, causing an electron
treatment of cancers of the lungs, esophagus, reproductive to be excited into a higher-energy orbital without changing
organs, brain, and head and neck. By the end of 1996, it its spin. This change creates a short-lived singlet state.
was estimated that tens of thousands of patients with The PS may return to its ground state by releasing heat
various types and stages of cancer had been treated with or light. Alternatively, it may transition to a triplet state
PDT. In Poland, the use of PDT began in 1986. Despite through intersystem crossing (ISC), where the electron
advances in cancer treatment over the past decades, cancer spin is reversed. The longer PS remains in the triplet state,
remains a major medical challenge, claiming millions of the greater the likelihood that it will encounter other
lives and negatively affecting the quality of life of survivors. molecules, leading to the formation of chemically reactive
The primary treatments for cancer remain chemotherapy compounds. There are two primary processes that occur
and radiotherapy, both of which have serious side effects.
Patients undergoing these treatments often report severe
pain. Consequently, finding alternative treatment regimens
that provide improvement in health status, with the
possibility of complete recovery and minimal to no side
effects, is a priority for clinicians and researchers. 3
This review explores various important aspects of
PDT, including its mechanism of action, and provides an
overview of its historical development. We also highlight the
promising results of photosensitizer (PS) use, combination
therapies, and the prospects these innovations bring. The
current directions of PDT are presented in Figure 1.
2. Mechanism of action of PDT
PDT relies on the concomitant presence of molecular
oxygen, a PS, and near-infrared or visible light. Each
of these ingredients is non-toxic on its own and does
not damage tissues or cells. Ideally, the PS is absorbed
and accumulates within the target cells. Since the PS is
harmless when not exposed to light, any potential toxicity Figure 1. Current directions of photodynamic therapy
Abbreviations: PS: Photosensitizer; PDT: Photodynamic therapy;
in PDT can be minimized by selectively illuminating only PTT: Photothermal therapy; ROS: Reactive oxygen species; h: Planck’s
specific areas. A PS absorbs light energy and transfers it constant; v: The frequency of light, O : Oxygen molecules.
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Volume 8 Issue 2 (2025) 17 doi: 10.36922/itps.4559