Thérapie photodynamique

Résumé

La thérapie photodynamique (ou photothérapie dynamique ; photochimiothérapie ; en photodynamic therapy, abrégée en PDT), est une technique de traitement médical local et sélectif visant à détruire des tissus pathologiques, ou certains microbes, grâce à l'utilisation de substances chimiques photosensibilisantes devenant cytotoxiques une fois activés par de une lumière (pour une gamme réduite de longueurs d'onde) ou dans certains cas par des rayons X (qui peuvent pénétrer en profondeur dans l'organisme). Cette méthode a pour avantages de ne laisser aucune trace ou cicatrice inesthétique, d'être mieux tolérée et moins couteuse que les chimiothérapies classiques, tout en ayant un potentiel d'effets mutagènes très faible. Histoire Au début du , Von Tappenier réussi à tuer des paramécies en utilisant l'acridine orange comme photosensibilisateur. Dans les années 1980, les thérapies photodynamiques se font surtout connaitre aux États-Unis, au Canada et au Japon où elles permett

Source officielle

https://fr.wikipedia.org/wiki/Th%C3%A9rapie_photodynamique

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QDs-Chlorine e6 conjugates in photodynamic therapy

Erol Basic

EPFL2006

Chargement

Optimization of the Distance between Cylindrical Light Distributors Used for Interstitial Light Delivery in Biological Tissues

Aurelien Stephen Arnaud Gregor, Georges Wagnières

Cylindrical light diffusers (CLDs) are often employed for the treatment of large tumors by interstitial photodynamic therapy (iPDT) and photoimmunotherapy (PIT), which involves careful treatment planning to maximize therapeutic dose coverage while minimizing the number of CLDs used. There is, however, a lack of general guidelines regarding optimal positioning of CLDs, in particular when they are inserted in parallel to treat head and neck squamous cell cancer (HNSCC). Therefore, the purpose of this study is to determine the CLD-CLD distances maximizing the necrosis for different geometries of CLD positions and shed light on the influence of different optical parameters on this distance, in particular when HNSCCs are treated by interstitial PIT with cetuximab-IR700 using up to seven CLDs. To that end, Monte-Carlo simulations of the light propagation around CLDs inserted perpendicularly in a semi-infinite tumor were performed to determine the volume receiving a fluence larger than a therapeutic threshold. An optimization algorithm was then used to calculate and maximize the necrosed tumor volumes. Tumor optical properties were derived from published data. Our findings suggest that optimal CLD positioning maximizing the volume of necrosed tumor during interstitial PIT for typical HNSCC optical properties corresponds to a CLD-CLD distance between 11.5- and 13-mm. Variations of the absorption and reduced scattering coefficients have the greatest influence on CLD placements, while tissue anisotropy factor, CLD insertion geometry, CLD length, and the angular dependence of the radiance emitted by the CLDs have minimal influence. At first approximation the influence of these optical parameters on optimal CLD-CLD distance are independent. Our data also suggests it is possible to derive new treatment plans using knowledge of previous treatment plans.

MDPI2022

Chargement

Various human pathologies, such as cancers or, notably, exudative age-related macular degeneration (AMD), are characterized by an abnormal vascular proliferation (angiogenesis), which in the case of this type of AMD, can rapidly lead to blindness if no countermeasures are taken. In the past few years, it has become possible to stop - or at least to notably slow down - the evolution of AMD, by applying treatments based on photodynamic therapy (PDT), whereby, through the action of a molecule acting as photosensitizer (PS) which is targeted preferentially to the choroidal neovessels (CNV), the effects of this abnormal angiogenesis are stopped by provoking the closure of the neovessels. In particular, the PDT group at EPF-Lausanne has, in the past, already tested on the model of the chick embryo chorioallantoic membrane (known as the CAM model) several PSs of potential interest as substitute to the product currently considered as standard (Visudyne® , itself co-developed in this group) for the treatment of the CNV associated with AMD. The aim of this thesis was to study new molecules and/or formulations, potentially suitable as substitutes to the current photodynamic treatment of AMD, while diminishing its negative side-effects: general phototoxicity due to diffusion of the product out of the vasculature and further lack of selectivity leading to (undesirable) partial occlusion of the normal vasculature. In order to enable extrapolation and comparison of the results obtained, we have focused our attention on vascular effects only and administered the tested PSs under essentially similar conditions (formulation in DMSO; same delivery system through biodegradable nanoparticles built with the same polymer). In addition, the same animal model (the CAM model) was used throughout the entire study, the formulations being administered by intravenous injection. This model, importantly, allows for an easy and real-time semi-quantitative visualisation and recording of the vascular effects of a PS induced during a PDT session. In the first part of this work, we demonstrate that the tetra-phenylporphyrin molecule, when formulated in nanoparticles based on poly(D, L - lactic acid, of well defined size (ca. 200 nm or less) is a very interesting PS-candidate potentially suitable as a replacement of the currently used one. We show that inclusion of this PS in nanoparticles notably reduces the PDT's general phototoxicity. We believe therefore that this PS would deserve more thorough pre-clinical studies, on an animal model closer to the human case (for example, Ryan's model). The second part of this thesis aimed at elaborating a strategy allowing, in due time, for an improved selectivity of occlusion of the neovasculature, said strategy aiming at an active targeting of neovessels. Recently, a number of possible biochemical targets have been identified, including the so-called ανβ3 receptors, which are highly expressed at the level of the neovessels' endothelial cells. Our approach consisted in coupling a fluorescent molecule (fluorescein, easily visualized by epi-microscopy) to a protein (a kistrin) which contains the RGD peptide sequence, known for its affinity for the ανβ3 receptors. We have thus been able to demonstrate that the kistrin was effectively linked to these receptors and, therefore, that active targeting of the neovessels had indeed taken place. A complete proof of this concept by realizing the coupling of this kistrin with a PS molecule will be the next step in this research.

EPFL2007

Chargement

Optimization of the Distance between Cylindrical Light Distributors Used for Interstitial Light Delivery in Biological Tissues

Aurelien Stephen Arnaud Gregor, Georges Wagnières

MDPI2022

EPFL2007