Cyclodextrin capped gold nanoparticles as a delivery vehicle for a prodrug of cisplatin

Yi Shi, Jerry Goodisman, James C. Dabrowiak

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

In this work, we explore the use of a quick coupling mechanism for "arming" a cyclodextrin coated gold nanoparticle (AuNP) delivery vehicle, 2, with an adamantane-oxoplatin conjugate that is a prodrug of cisplatin, 3, to produce a cytotoxic nanodrug, 4. The two-part arming system, which utilizes the well-known guest-host interaction between β-cyclodextrin and adamantane, may be useful for rapidly constituting polyfunctional nanodrugs prior to their application in chemotherapy. The 4.7 ± 1.1 nm delivery vehicle, 2, coated with per-6-thio-β-cyclodextrin (βSCD), was characterized using transmission electron microscopy and absorption spectroscopy, and the density of surface-attached βSCD molecules, ∼210 βSCD/AuNP, was determined using thermogravimetric analysis. Because 13C NMR spectra of βSCD used in the study exhibited disulfide linkages and the observed surface density on the AuNP exceeded that possible for a close-packed mono layer, a fraction of the surface-attached βSCD molecules on the particle were oligomerized through disulfide linkages. Determination of the binding constant, K, for the 3-βCD interaction using 1H NMR chemical shifts was complicated by the self-association of 3 to form a dimer through its conjugated adamantane residue. With a dimerization constant of K2 = 26.7 M-1, the value of K for the 3-βCD interaction (1:1 stoichiometry) is 400-800 M-1, which is lower than the value, K = 1.4 × 103 M-1, measured for the 2-3 interaction using ICP-MS. Optical microscopy showed that when neuroblastoma SK-N-SH cells are treated with the nanodrug, 4 (2+3), clusters of gold nanoparticles are observed in the nuclear regions of living cells within 24 h after exposure, but, at later times when most cells are dying or dead, clustering is no longer observed. Treating the cells with 4 for 72 h gave percent inhibitions that are lower than that of cisplatin, suggesting that the Pt(IV) ions in 4 may be incompletely reduced to cytotoxic Pt(II) species in the cell.

Original languageEnglish (US)
Pages (from-to)9418-9426
Number of pages9
JournalInorganic Chemistry
Volume52
Issue number16
DOIs
StatePublished - Aug 19 2013

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Adamantane
Prodrugs
Cyclodextrins
Gold
Cisplatin
delivery
vehicles
gold
Nanoparticles
Disulfides
nanoparticles
disulfides
Electron absorption
cells
Nuclear magnetic resonance
linkages
Molecules
Chemotherapy
Dimerization
Chemical shift

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Cyclodextrin capped gold nanoparticles as a delivery vehicle for a prodrug of cisplatin. / Shi, Yi; Goodisman, Jerry; Dabrowiak, James C.

In: Inorganic Chemistry, Vol. 52, No. 16, 19.08.2013, p. 9418-9426.

Research output: Contribution to journalArticle

Shi, Yi ; Goodisman, Jerry ; Dabrowiak, James C. / Cyclodextrin capped gold nanoparticles as a delivery vehicle for a prodrug of cisplatin. In: Inorganic Chemistry. 2013 ; Vol. 52, No. 16. pp. 9418-9426.
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