Adamantane-platinum conjugate hosted in β-cyclodextrin: Enhancing transport and cytotoxicity by noncovalent modification

Deepali Prashar, Yi Shi, Debjyoti Bandyopadhyay, James C Dabrowiak, Yan Yeung Luk

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

This work reports the synthesis of a complex of a carboplatin analog having tethered adamantane that is encapsulated in the hydrophobic cavity of β-cyclodextrin (βCD) and its cytotoxic activity towards human neuroblastoma cells (SK-N-SH). We found that this inclusion complex of βCD adamantane carboplatin analog exhibited higher cytotoxicity towards SK-N-SH cells than carboplatin itself, and the inclusion complex exhibited a higher binding to plasmid pBR322 deoxyribonucleic acid (DNA) than carboplatin. Confocal fluorescence images of SK-N-SH cells treated with βCD having an attached fluorescein isothiocyanate (FITC)-tag exhibited fluorescence in the vicinity of the nuclei of the neuroblastoma cells. Direct measurements of the platinum content in SK-N-SH cells using inductively coupled plasma mass spectrometry (ICP-MS) indicated that the uptake rate of carboplatin was about 4 times higher than βCD adamantane carboplatin analog inclusion complex. When compared to carboplatin, we believe that the higher cytotoxicity of inclusion complex towards SK-N-SH cells is due to its higher DNA binding ability as compared to carboplatin, and more efficient delivery to the nucleus of the cell. This work suggests that the advantage of deliberate noncovalent modification with βCD through host-guest chemistry may also be broadly applicable to other anticancer agents as well.

Original languageEnglish (US)
Pages (from-to)7421-7425
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number24
DOIs
StatePublished - Dec 15 2011

Keywords

  • Anticancer agents
  • Cyclodextrins
  • DNA
  • Host-guest chemistry
  • Noncovalent modification
  • Solvation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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