Cyclodextrin Capped Gold Nanoparticles as a Delivery Vehicle for a Prodrug of Cisplatin

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 (13)C 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 (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-βCD 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.

The state-of-play and future of platinum drugs

“…5). The platin drug is modified with an adamantine ligand, which forms a hostguest complex with the cyclodextrin by binding within its cavity (Shi et al 2013).…”

Gold Nanoparticles Interacting with β-Cyclodextrin–Phenylethylamine Inclusion Complex: A Ternary System for Photothermal Drug Release

“…The use of various cyclodextrins for the synthesis of AuNPs has been previously reported [72][73][74] . Furthermore, numerous nanometric systems have been designed, in which AuNPs are covered by modified CDs for potential biological applications [23][24][25][75][76][77] .…”

Rational Design of Multifunctional Gold Nanoparticles via Host–Guest Interaction for Cancer-Targeted Therapy

“…For instance, cyclodextrin-modified gold nanoparticles have been applied to construct versatile platform via host−guest interaction for targeted drug delivery conveniently. 31,32 Herein, a multifunctional nanocomposite based on β-cyclodextrin-modified gold nanoparticle (AuNP@CD) was delicately designed and fabricated for cancer-targeted therapy with intracellular pH-triggered drug delivery. As shown in Scheme 1, the peptidic derivative adamantane−PEG 8 −glycine− arginine−glycine−aspartic−serine (AD-PEG 8 -GRGDS) and the adamantane conjugated anticancer drug doxorubicin with hydrazone bond linkage (AD-Hyd-DOX) were decorated on the surface of AuNP@CD via host−guest interaction simultaneously, forming multifunctional nanocomposite AuNP@CD-AD-DOX/RGD.…”