Abstract
Photodynamic therapy (PDT) is a clinical modality used to treat cancer and infectious diseases. The main agent is the photosensitizer (PS), which is excited by light and converted to a triplet excited state. This latter species leads to the formation of singlet oxygen and radicals that oxidize biomolecules. The main motivation for this review is to suggest alternatives for achieving high-efficiency PDT protocols, by taking advantage of knowledge on the chemical and biological processes taking place during and after photosensitization. We defend that in order to obtain specific mechanisms of cell death and maximize PDT efficiency, PSes should oxidize specific molecular targets. We consider the role of subcellular localization, how PS photochemistry and photophysics can change according to its nanoenvironment, and how can all these trigger specific cell death mechanisms. We propose that in order to develop PSes that will cause a breakthrough enhancement in the efficiency of PDT, researchers should first consider tissue and intracellular localization, instead of trying to maximize singlet oxygen quantum yields in in vitro tests. In addition to this, we also indicate many open questions and challenges remaining in this field, hoping to encourage future research.
Highlights
Photodynamic therapy (PDT) relies on the combination of a photosensitizer (PS), light, and oxygen [O2(3Σg−)] to eliminate unwanted cells
This shows that, in the same way as we should look for desirable targets for PDT, it is necessary to understand which reactions should be avoided in order to control possible side effects and cell death mechanisms
In the previous sections of this review, we presented an overview on the mechanisms taking place in PDT, discussed possible targets of photooxidative damage, ways to aim for them and potential manners to maximize PDT efficiency
Summary
Photodynamic therapy (PDT) relies on the combination of a photosensitizer (PS), light, and oxygen [O2(3Σg−)] to eliminate unwanted cells. In spite of these advantages and the growing knowledge on the efficiency of PDT, it is evident that this clinical modality is still not widespread This can be attributed in part to a lack of knowledge on some of the molecular mechanisms taking place on PDT. We present some aspects that are still missing to create a clear mechanistic view of PDT and pinpoint possible approaches to overcome the challenges remaining on this field We believe that this analysis may help to understand which factors should be considered when developing an improved PDT protocol and reinforces the need of tailor-made
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