Photodynamic Therapy: A Compendium of Latest Reviews

Abstract

Photodynamic therapy (PDT) is a promising therapy against cancer. Even though it has been investigated for more than 100 years, scientific publications have grown exponentially in the last two decades. For this reason, we present a brief compendium of reviews of the last two decades classified under different topics, namely, overviews, reviews about specific cancers, and meta-analyses of photosensitisers, PDT mechanisms, dosimetry, and light sources. The key issues and main conclusions are summarized, including ways and means to improve therapy and outcomes. Due to the broad scope of this work and it being the first time that a compendium of the latest reviews has been performed for PDT, it may be of interest to a wide audience.

Keywords: cancer; meta-analysis; overview; photodynamic therapy; review.

Figure 1

Number of articles per year as a result of the search in the Scopus database (Elsevier). The search was restricted to only the titles of the articles (not restricted to review articles). Queries for each line were: TITLE (“photodynamic therapy”) red line; TITLE (“photodynamic therapy”) AND SUBJAREA (MEDI) green line; TITLE (“photodynamic therapy”) AND SUBJAREA (MATE) purple line. Note that the subject area is overlapped in some journals (materials and medicine are selected because they are more differentiated). Inset shows the difference in articles between Photodynamic Action (PA, dark symbol) and Photodynamic Therapy (red symbol).

Figure 2

A generalized diagram depicting the use of a brachytherapy-type template and transrectal ultrasound to precisely guide catheters containing fibre optics to the prostate gland for PDT. Reproduced with permission from M. Osuchowski, Photodiagnosis Photodyn. Ther. 2021 [73].

Figure 3

Clinical imaging assistance as an essential step in therapeutic planning. Left side: Two strategies suggested depending on the stage, size, and localization of the tumour. An interstitial PDT (iPDT) or, after a minimally invasive craniotomy, a photodiagnosis (PD) followed by a fluorescence-guided resection (FGR) and completed by an intraoperative PDT. Right side: Clinical imaging assistance plays an essential role in brain tumour PDT, including estimating the initial tumour volume, 3D treatment planning (light dose according to the volume geometry), and outcome assessment. Computed 3D image-based treatment planning provided reproducible data-based tumour volumes, stereotactic accuracy for tumour volume resection, and interstitial light fibre insertion for iPDT. Optical fibres for PDT can be placed under contrast-enhanced computed tomography (CT) guidance, and the surgical approach and trajectories can be planned using preoperative diffusion magnetic resonance imaging (MRI), CT imaging, and/or single-photon emission computed tomography (SPECT) images to achieve precise tumour localization, realize a minimally invasive craniotomy, and minimize controlateral brain injury. Reproduced with permission from D. Bechet, Cancer Treat. Rev. 2014 [88].

Figure 4

General design of 3rd generation PS: (a) conjugation of second-generation PS with targeting moiety; (b) encapsulation of the second generation into carriers (liposomes, micelles, and nanoparticles). Reproduced with permission from Ivan S. Mfouo-Tynga et al., Photodiagnosis and Photodynamic Therapy; published by Elsevier, 2021 [124].

Figure 5

Bioconjugation strategies in photodiagnosis (PD) and therapy (PDT) of cancer. An ideal target, such as tissue factor (also known as CD142), should be commonly yet selectively expressed by multiple tumour compartments, including but not limited to cancer cells, cancer stem cells, and tumour vascular endothelial cells (VCEs), whereas it is negatively, minimally, or restrictedly expressed in normal cells. A potentially new bioconjugation strategy is the use of recombinant DNA techniques to produce fusion proteins that contain a targeting domain and a fluorescent protein PS simultaneously for targeted PD and PDT. Reproduced with permission from S. Gomez et al., Molecules; published by MDPI, 2020 [125].

Figure 6

Cell death pathways in PDT. The mode of cell death observed after PDT depends to some extent on the intracellular localization of the PS and PDT-related damage to that organelle. PDT with PS localized in mitochondria will lead to loss of membrane permeability and release of pro-apoptotic mediators, while ER damage will release cellular deposits of calcium. PS that accumulates in lysosomes will release proteolytic enzymes upon illumination. Lysosomes may also fuse with autophagosomes to hydrolyse-damaged organelles and recycle them during autophagy. In the case of excess of damage, the cell will not survive despite the initiation of autophagy. Necrosis and autophagy may be dominant cell death modes after PDT when apoptosis is dysfunctional. It should be remembered that several PS may localize in more than one organelle, and the activation of cell death pathways may occur concurrently. Reproduced with permission from Pawel Mroz et al., Cancers; published by MDPI, 2011 [157].

Figure 7

The shift from preclinical evaluation, through Phase I, II, and III clinical trials, and finally to accepted clinical practice is illustrated, with the advocated shifts in dosimetry goals throughout the pathway. While a comprehensive dosimetry approach might be used in preclinical work to mechanistically inform practice, the transition to Phase I trial requires that reasonably efficient methods of dosimetry be implemented, and in the future, the goal should be to shift towards treatment-limiting dosimetry and correlated surrogates. Eventually, these might become the required dosimetry in approved/cleared treatments, going beyond basic prescriptions of light and drug doses. The image and caption are reproduced from their original created by Pogue, B.W. et al., Phys. Med. Biol. 2016, 61, R57–R89 (doi:10.1088/0031-9155/61/7/R57) [194] under Creative Commons Attribution 3.0.