Please cite this article in press as: G. Marcelo, et al., Interaction of gold nanoparticles with Doxorubicin mediated by supramolecular chemistry, Colloids Surf. B: Biointerfaces (2015), http://dx.doi.org/10.1016/j.colsurfb.2015.01.041 ARTICLE IN PRESS G Model COLSUB-6874; No. of Pages 8 Colloids and Surfaces B: Biointerfaces xxx (2015) xxx–xxx Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces j o ur nal ho me pa ge: www.elsevier.com/locate/colsurfb Interaction of gold nanoparticles with Doxorubicin mediated by supramolecular chemistry Gema Marcelo ∗ , Ekrem Kaplan 1 , M. Pilar Tarazona, Francisco Mendicuti ∗ Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Alcalá de Henares 28871, Madrid, Spain a r t i c l e i n f o Article history: Received 29 November 2014 Received in revised form 21 January 2015 Accepted 23 January 2015 Available online xxx Keywords: Catechol Cyclodextrin Gold nanoparticles Doxorubicin Drug release Polymer a b s t r a c t A copolymer containing -cyclodextrin, catechol and polyethylene glycol groups in its side chain was designed for the in situ synthesis and coating of gold nanoparticles (Au@PEG–CD NPs). These platforms were designed as a smart carrier and traceable delivery probe of the chemotherapeutic Doxorubicin drug (Dox). The coated polymer forms stable complexes with Dox in water with a high binding constant (K = 2.3 × 10 4 M −1 at 25 ◦ C), which is one hundred times greater than those reported for its complexation with native CD. Therefore, Au@PEG–CD NPs were able to load 0.01 mg of the drug per mg of NP and to release up to 60% of it in 48 h at 37 ◦ C. In addition, Au@PEG–CD NPs had the capacity to act as a quencher of Dox fluorescence when it was complexed with CD in the NP organic shell. This feature allows the Dox release to be tracked by monitoring the recovery of its fluorescence in real time. Therefore, the Dox release kinetics and the influence of temperature on the thermal stability of Dox/CD complexes on Au@PEG–CD NP were investigated. The increase in temperature favors the dissociation of the complexes and sub- sequent Dox release from the NP. The first order rate constant for drug releasing was 1.1 × 10 −2 min −1 with a half-life time of 63 min at 37 ◦ C. Finally, the great potential of the carrier/probe double nature of Au@PEG–CD NPs was demonstrated in real time inside HeLa cells. © 2015 Elsevier B.V. All rights reserved. 1. Introduction Doxorubicin (Dox) is a chemotherapeutic drug used in the treat- ment of a wide variety of cancer types. As with many other drugs, its low water solubility and poor photostability are drawbacks that need to be solved along with the side effects related to its citotoxic- ity. In order to overcome these limitations Dox has been introduced in different carriers [1–4]. Among these different vectors, gold nanoparticles (Au NPs) are receiving great attention because of their relatively easy surface functionalization [5] and adequate cell penetration [6]. Moreover, Au NPs are known for their optical prop- erties derived from the localized surface plasmon resonance (LSPR), which have a strong impact on a wide range of bioapplications such as imaging, sensing and photothermal therapy [7–9]. An interest- ing feature is related to the effects that Au NPs induce on organic dye fluorescence properties [10–12]. Au NPs have mostly been reported to act as a dye fluorescence quencher. However, this abil- ity is strongly dependent on the Au NP-dye distance, among other ∗ Corresponding authors. Tel.: +34 918854672. E-mail addresses: gema.marcelo@uah.es (G. Marcelo), francisco.mendicuti@uah.es (F. Mendicuti). 1 Current address: Istanbul Technical University, Science and Letters Faculty, Chemistry Department, 34469 Maslak, Istanbul, Turkey. factors [12]. This behavior renders Au NPs great potential to be used as probes in the monitoring of different biomedical processes such as drug delivery and the determination of key molecules associated to important diseases. For example, Wang et al. [13] and El-Sayed et al. [14] described how Au NPs that bind Dox with an acid-labile linkage, allow the release of Dox into the cell acid lysosomes to be tracked by a recovery of Dox fluorescence after the breaking of the linkage. In another work, Lee et al. used Au NPs functionalized with Cy5.5 to monitor the activity of a protease involved in cancer in vivo. Upon interaction with the protease, the linkage between Cy5.5 and the Au NP breaks off, leading to the recovering of the Cy5.5 fluorescence [15]. On the other hand, cyclodextrins (CDs) are natural cyclic oligosaccharides formed of glucopyranose units. They possess a basket-shaped topology with an inner cavity which exhibits relatively hydrophobic behavior. CDs are able to form reversible, non-covalent inclusion complexes in aqueous media with a wide variety of hydrophobic guests with dimensions that fit inside their cavities. Complexation favors guest solubilization and stability allowing CDs to be used as drug carrier/delivery systems [16]. In addition, complexation processes are usually accompanied by a negative enthalpy change [17], and consequently the amount of the drug released could be increased with temperature, as well as the rate of the process. Another advantage of using CDs as http://dx.doi.org/10.1016/j.colsurfb.2015.01.041 0927-7765/© 2015 Elsevier B.V. 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