Cyclodextrin capped gold nanoparticles as a delivery vehicle for a prodrug of cisplatin.
Inorg Chem
; 52(16): 9418-26, 2013 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-23889547
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 ß-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-ß-cyclodextrin (ßSCD), was characterized using transmission electron microscopy and absorption spectroscopy, and the density of surface-attached ßSCD molecules, â¼210 ßSCD/AuNP, was determined using thermogravimetric analysis. Because (13)C NMR spectra of ßSCD 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 ßSCD molecules on the particle were oligomerized through disulfide linkages. Determination of the binding constant, K, for the 3-ßCD interaction using (1)H 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-ßCD interaction (1:1 stoichiometry) is 400-800 M(-1), which is lower than the value, K = 1.4 × 10(3) 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
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Pró-Fármacos
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Cisplatino
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Ciclodextrinas
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Nanopartículas Metálicas
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Ouro
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Inorg Chem
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos