Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

Abstract

This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from CNAs were analyzed. The cell cytotoxicity of CNA formulations was similar to free Ru complexes despite reduced or eliminated DNA interactions. The release rate and the amount of each Ru complex released (%) varied inversely with complex hydrophobicity, while the effect of solution ionic strength was dependent on complex hydrophobicity. Premature release of two photoactivatable prodrugs prior to irradiation was believed to account for higher activity in cells studies compared to DNA interaction studies; however, for photostable 1O2 generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 hrs. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.

An overview of photosubstitution reactions of Ru(II) imine complexes and their application in photobiology and photodynamic therapy

“…Related strained complexes were recently incorporated into cross-linked polymeric nanoassemblies to tune the hydrophobicity, photochemical activation, pH, and solution ionic strength in metal complex photodelivery. 115 Additionally, [Ru(bpy) 2 (Me 2 dppz)] 2+ also acts as a photochemical DNA sensor due to the DNA light-switch behavior of dppz-type ligands. 114 In polar protic solvent, the lowest energy excited state is a dark state, but when intercalated into DNA (or in nonpolar solvent), the dark state is higher in energy compared to the bright state.…”

Functionalized Flexible Soft Polymer Optical Fibers for Laser Photomedicine

“…Recently, a growing interest on photomedicine is the optogenetics which requires delivering light to stimulate and/or control neuron and proteins . Such light delivery applications involve fluorescent probes, bioluminescent proteins, and light‐sensitive polymers to generate and emit localized light. In biomedical diagnostics and therapeutics, increasing light transmission efficiency through the biological tissue remains a challenge due to intrinsic light scattering and absorption .…”

The Thermodynamic Effects of Ligand Structure on the Molecular Recognition of Mononuclear Ruthenium Polypyridyl Complexes with B‐DNA

“…Both KP1019 and NAMI‐A are thought to be activated by reduction to Ru II complexes in cells, however it is not clear how they act beyond this with activity postulated in the mitochondria, endoplasmic reticulum and even possibly in the nucleus . Compared to platinum drugs, these ruthenium complexes are often identified as less toxic and capable of overcoming the resistance induced by platinum drugs in cancer cells …”

“…[1][2][3] Compared to platinum drugs, these ruthenium complexes are often identified as less toxic and capable of overcoming the resistance induced by platinum drugs in cancer cells. [4][5][6][7] More recently, the ruthenium polypyridyl complexes (RPCs), [(phen) 2 Ru(tatpp)]Cl 2 (3Cl 2 ) and [(phen) 2 Ru(tatpp)Ru(phen) 2 ]Cl 4 (4Cl 4 ) have also shown promising anti-cancer activity with observed DNA cleavage activity in vitro, selective cytotoxicity towards malignant cultured human cell lines, and demonstrable tumor regression in animal tumor models. [7] Note: When the numerical abbreviation for RPCs in this work is indicated as a charged species, i.e.…”