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Modulation of Photosensitization Processes for an Improved Targeted Photodynamic Therapy

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Abstract:

Photodynamic therapy (PDT) is a cancer treatment modality involving the combination of light, a photosensitizer (PS) and molecular oxygen, which results in the production of cytotoxic reactive oxygen species (ROS). Singlet oxygen (1O2) is one of the most important of these ROS. Because the lifetime and diffusion of 1O2 is very limited, a controllable singlet oxygen generation with high selectivity and localization would lead to more efficient and reliable PDT. The lack of selective accumulation of the PS within tumour tissue is a major problem in PDT. Targeted PDT would offer the advantage to enhance photodynamic efficiency by directly targeting diseased cells or tissues. Many attempts have been made to either selectively deliver light to diseased tissues or increase the uptake of the photoactive compounds by the target cells. The review will survey the literature regarding the multi-level control of 1O2 production for PDT applications. The mechanisms of ROS formation are described. The different strategies leading to targeted formation of 1O2 are developed. Some active PDT agents have been based on energy transfer between PS by control of the aggregation/ disaggregation. The concept of molecular beacon based on quenching-dequenching upon protease cleavage is capable of precise control of 1O2 by responding to specific cancer-associated biomarkers.





Keywords: 1,4-diazabicyclo[2,2,2]octane; 2,2,6,6-tetraethyl-4-piperidone; Asparagine; B16 melanoma; BT breast carci-noma cells; Black Hole Quencher 3; Carotenoids; Fibroblast activation protein (FAP); Goeppert-Mayer; N,N-dimethyl-4-nitrosoaniline; Neuropilin-1; Photodynamic therapy; Photodynamic therapy (PDT); Protoporphyrin IX; R-thrombin; Reactive oxygen species; Tumour; Vibrational relaxation; aggregation; azomethine dyes; cardiovascular; carotenoid; cathepsin B; chemotactic molecules; collagenases; coreceptor neuropilin-1 (NRP-1); coupled multiple chlorin e6 (Ce6); dermatolog-ical; dye-sensitized photooxygenations; electrostatic effects; fluorescence quencher; gelatinases; glioblastoma; higher occupied molecular orbital (HOMO); human embryonic kidney cells (HEK293); intersystem crossing (ISC); intratumoural hypoxic state; lactic acid; lipophilic characteristic; lowest unoccupied molecular orbital (LUMO); matrilysins; matrix metalloproteinases, MMPs; molecular beacon; nanoagent; neovascularization; oligonucleotide; ophthalmic; oxyradicals; pharmacophore; photoactive compounds; photochemical; photodynamic efficiency; photophysical; photoprotective; photosensi-tizer; photosensi-tizer (PS); photosensitizing; phthalocyanine; porphyrin; pro-vitamin A; pyropheophorbide; pyropheophorbide (Pyro); quenchers; reactive oxygen species (ROS); single-walled carbon nanotubes (SWNT); stem-loop structure (hairpin); stilbene quinones; stromelysins; targeting; tissue inhibitors of metalloproteinases (TIMPs); transmembrane; triplet state (T1); tumour neovasculature; urokinase plasminogen activator (uPA); vascular-targeting; xenographic tu-mour model

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710793205453

Publication date: November 1, 2010

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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