Abstract
In this Minireview, we highlight recent advances in the design of transition metal complexes for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT), and discuss the challenges and opportunities for the translation of such agents into clinical use. New designs for light‐activated transition metal complexes offer photoactivatable prodrugs with novel targeted mechanisms of action. Light irradiation can provide spatial and temporal control of drug activation, increasing selectivity and reducing side‐effects. The photophysical and photochemical properties of transition metal complexes can be controlled by the appropriate choice of the metal, its oxidation state, the number and types of ligands, and the coordination geometry.
Highlights
Introduction candidates for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT)More general comprehensive reviews are available elsewhere.[6]Nature uses light to promote and control some of the most crucial reactions, from photosynthesis, converting light and carbon dioxide to oxygen and sugar, to the synthesis of 2
Liu and coblood serum protein, ca. 0.6 mm) made polycationic and workers synthesised a poly-phenanthroline RuII photosensidecorated with multiple triphenylphosphonium (TPP) groups tizer with 3 pendant cyclodextrin groups which strongly to target mitochondria, and polyethylene oxide (PEO) chains associate with adamantane-functionalized transferrin moleto improve water solubility.[15]
We have focussed in this Minireview on new designs for photochemotherapeutic transition metal anticancer complexes which have emerged recently, including octahedral IrIII PDT photosensitizers and PtIV PACT agents, both of which have classical inert low-spin 5d6 configurations
Summary
Owing to their abundant and ubiquitous presence in cells and to their reactivity towards 1O2 and other ROS, proteins are generally regarded as the main target of photodynamic therapy, followed by lipids and nucleic acids.[10]. Complex 6 exhibited sub-micromolar IC50 values towards 3D multi-cellular tumor spheroids (models for solid tumors) when irradiated with 750 nm two-photon near infrared light Their effects on proteins in A549 lung cancer cells, was investigated using liquid chromatography-tandem mass spectrometry, which revealed specific oxidation of histidine residues to 2-oxo-His in the key proteins aldose reductase and heat-shock protein-70 (Hsp-70) after photoactivation of complex 6. The oxidative stress induced during the photoactivation increased the levels of enzymes involved in the glycolytic pathway This might arise from a switch in energy (ATP) production from oxidative phosphorylation (reduction of O2 to H2O in mitochondria) to glycolysis (conversion of glucose to pyruvate in the cytoplasm). The results suggest that iridium complexes might target specific proteins in cancer cells and induce oxidation irreversibly upon photoactivation, contributing to efficient PDT. ROS generation resulted in protein dysfunction and triggered cancer cell death
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