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

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...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2016-01, Vol.4 (3), p.394-48
Main Authors: Dickerson, Matthew, Howerton, Brock, Bae, Younsoo, Glazer, Edith
Format: Article
Language:English
Subjects:
Biotechnology
Chemical compounds
Crosslinking
Deoxyribonucleic acid
Hydrophobicity
Nanostructure
Ruthenium
Strength
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Summary: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 1 O 2 generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 h. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible. Cross-linked polymeric nanoassemblies are potential carrier systems for cytotoxic ruthenium complexes, and exhibit a combination of electrostatic and hydrophobic interactions with the metal complexes that impact release rates, release percentages, and biological activity.
ISSN:2050-750X
2050-7518
DOI:10.1039/c5tb01613d