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

Matthew Dickerson, Brock Howerton, Younsoo Bae, Edith C. Glazer

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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 h. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.

Original languageEnglish
Pages (from-to)394-408
Number of pages15
JournalJournal of Materials Chemistry B
Volume4
Issue number3
DOIs
StatePublished - 2016

Bibliographical note

Funding Information:
This work was made possible through the support of the American Cancer Society (RSG-13-079-01-CDD). MD acknowledges the University of Kentucky Cancer Nanotechnology Training Center (UK-CNTC) postdoctoral traineeship, supported by the NCI/NIH and part of the National Cancer Institute Alliance for Nanotechnology in Cancer (5R25CA153954).

Publisher Copyright:
© 2016 The Royal Society of Chemistry.

ASJC Scopus subject areas

  • Chemistry (all)
  • Biomedical Engineering
  • Materials Science (all)

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