In Situ Visualization of the Local Photothermal Effect Produced on α-Cyclodextrin Inclusion Compound Associated with Gold Nanoparticles
© Silva et al. 2016
Received: 6 December 2015
Accepted: 13 February 2016
Published: 7 April 2016
Evidence of guest migration in α-cyclodextrin-octylamine (α-CD-OA) inclusion compound (IC) generated via plasmonic heating of gold nanoparticles (AuNPs) has been studied. In this report, we demonstrate local effects generated by laser-mediated irradiation of a sample of AuNPs covered with inclusion compounds on surface-derivatized glass under liquid conditions by atomic force microscopy (AFM). Functionalized AuNPs on the glass and covered by the ICs were monitored by recording images by AFM during 5 h of irradiation, and images showed that after irradiation, a drastic decrease in the height of the AuNPs occurred. The absorption spectrum of the irradiated sample showed a hypsochromic shift from 542 to 536 nm, evidence suggesting that much of the population of nanoparticles lost all of the parts of the overlay of ICs due to the plasmonic heat generated by the irradiation. Mass spectrometry matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) performed on a sample containing a collection of drops obtained from the surface of the functionalized glass provided evidence that the irradiation lead to disintegration of the ICs and therefore exit of the octylamine molecule (the guest) from the cyclodextrin cavity (the matrix).
KeywordsGold nanoparticles Plasmonic heating Cyclodextrin inclusion compound Guest migration
Due to the strong electric fields at the surface, absorption and scattering of electromagnetic radiation by noble metal nanoparticles is enhanced robustly. These unique properties provide the potential for designing novel optically active reagents. The use of nanoparticles in medicine is one of the important directions being taken by current research in nanotechnology. Their applications in drug delivery, cancer cell diagnostics and therapeutics have been the active fields of research [1–6]. Plasmon resonance of gold nanostructures is of great interest for photothermal properties and optical imaging due to their remarkable capacity to absorb and scatter light at visible and near-infrared (near-IR) regions. These optical properties depend on the nanoparticle size, shape, and dielectric environment and enable their application in novel imaging techniques and as sensing probes [1, 2, 7, 8]. Gold nanoparticles (AuNPs) convert optical energy into heat via non-radiative electron relaxation dynamics, which endow them with intense photothermal properties. These localized heating effects can be directed toward the eradication of diseased tissue, providing a non-invasive alternative to surgery. Colloidal gold is well known to be biologically inert and has been used in vivo since the 1950s, particularly as an adjuvant in radiotherapies; however, the use of these nanoparticles as photothermal agents is relatively recent . Additionally, AuNPs are useful for drug delivery by using laser irradiation to control spatial and temporal drug release .
On the other hand, in the nanoscience field, cyclodextrins (CDs) have been used to prepare AuNPs capped with thiolated α- and β-CDs  for the formation of AuNPs by femtosecond laser ablation  and also to prepare AuNPs by chemical reduction in presence of unmodified CDs . The CD-ICs, particularly those leading to supramolecular self-assemblies, continue to be a fascinating topic in modern organic chemistry because they serve as models for understanding molecular recognition [13–16] and as precursors for designing novel nanomaterials .
In solid α-CD-ICs with alkylated guests, the functional group of the guest molecule may be located at the extreme boundary of a CD unit in the electron-dense space, and the alkyl chain may be located in the apolar and electron-poor zone of the CD cavities [18–20]. These functional groups (–SH, –COOH, –NH2) are available to interact with the particles thus stabilizing them .
The migration of alkyl thiol molecules included in the cavities of the channel-type structure of α-CD-IC in the presence of AuNPs by powder X-ray diffraction has been reported .
Synthesis of Colloidal AuNPs
The gold colloid was synthesized based on the Turkevich method with slight modifications . Prior to the synthesis, all glassware was thoroughly cleaned by soaking in aqua regia (comprising 3 parts HCl (Merck) to 1 part HNO3 (Merck)) and rinsing with Milli-Q water (18 MΩ Millipore Nanopure purification system).
In a 250-mL round-bottom flask equipped with a condenser, 100 mL of an aqueous HAuCl4 solution (1 mM) (HAuCl4·3H2O; Sigma-Aldrich) was brought to a rolling boil with vigorous stirring. As quickly as possible, 10 mL trisodium citrate dihydrate (Na3C6H5O7·2H2O; Sigma-Aldrich) solution (38.8 mM) was added to the solution with constant stirring. The solution was heated for an additional 30 min and left at room temperature. The solution was then filtered through a 0.45-μm filter membrane of cellulose acetate thus obtaining 12-nm diameter AuNPs.
ICs were obtained using octylamine (OA; Sigma-Aldrich) and a saturated solution of α-cyclodextrin (α-CD; Sigma-Aldrich) in Milli-Q water at room temperature. The amine/cyclodextrin molar ratios used in the experiments were 2:1. The crystals were filtered and dried under vacuum [27, 28].
Samples were prepared following protocols described previously [29–31]. The glass slides (1 cm × 1 cm) were cleaned for 30 min in a bath “piranha solution” comprising 4 parts sulfuric acid (H2SO4; Merck) to 1 part hydrogen peroxide (H2O2; Merck) at 60 °C. After rinsing with methanol (CH3OH) spectrophotometric grade (Merck), the slides were dipped for 24 h in vials containing (3-aminopropyl)-trimethoxysilane (APTMS; Sigma-Aldrich) in CH3OH solution (1 APTMS:4 CH3OH).
The slides were rinsed with Milli-Q water and immersed in colloidal gold solution at room temperature for 24 h. A final Milli-Q water rinse concluded the derivatization process.
AuNP IC Conjugation
The functionalized slides with AuNPs were immersed in IC solution in dimethyl sulfoxide (DMSO; Sigma-Aldrich) (prepared from dissolving IC crystals) for 24 h. Finally, the slides were rinsed with Milli-Q water.
Irradiation of the Functionalized Glass with AuNPs and Conjugation to the IC
A water drop was added to the IC/conjugated glass, and the system was irradiated using a continuous wave laser (532 nm wavelength, potency 45 mW) for 5 h.
Atomic Force Microscopy (AFM)
Experiments were performed to determine changes in height of the particles during the several stages of glass functionalization. All measurements were performed in situ at room temperature using a MultiMode with electronic NanoScope V (Bruker) with an incorporated fluid cell. The images were obtained in PeakForce Tapping mode, using SNL model probes from Bruker, a spring constant of 0.35 N/m, and nominal tip radius of curvature of 10 nm. The scan-line speed was optimized to between 0.5 and 1 Hz with a pixel number of 512 × 512.
AFM micrographs were recorded every 15 min, over a sample irradiated in situ for a total period of 5 h, the time it took for the drop to vaporize (Additional file 1: Figure S1).
A Shimadzu UV-3101PC spectrophotometer was used. Spectra were recorded at between 200 and 700 nm by installing the slide directly onto the sample holder with barium sulfate (BaSO4), and using an APTMS-derivatized slide as a blank. The results of the diffuse reflectance were transformed to absorbance units using Kubelka-Munk’s conversion.
Mass Spectrometry Analysis of the Water Drop After Irradiation
Mass spectra were generated using a MALDI-TOF Microflex (Bruker Daltonics Inc., MA, USA) instrument in a positive ion mode, using detection by reflection to obtain the spectra. Samples were mixed with a 2,5-dihydroxybenzoic acid (DHB) matrix in a 1:1 ratio, and 2 μL of each mix was deposited on a micro scout simple-holder slide.
Analysis of mass spectra was performed using the program Flex Analysis v. 2.2 version 2.2 (Bruker Daltonik GmbH, Germany).
Results and Discussion
AFM Monitoring the Effect of Irradiation on ICs Supported on Functionalized Glass Slides
To study the effects of the irradiation on the functionalized glass slides containing the IC-covered AuNPs, a drop of water was added to the sample, which was then irradiated continuously and monitored by recording AFM images during the 5 h of the irradiation process. The micrograph (Fig. 3d) shows that after irradiation, a drastic decrease in the height of the AuNPs covered by IC occurred (the histogram shows absence of structures in the range of 22 to 34 nm) which indicates that IC has been detached from the surface. However, the particles remained anchored and not aggregated on the surface after irradiation.
Additionally, we observed an increase in the population of particles at between 10 and 15 nm, which are similar to the heights obtained in the glass functionalized with AuNPs only. This finding is consistent with the theory that the majority of nanoparticles lost all of the parts of overlaid IC due to the plasmonic heat generated by the irradiation.
This phenomenon was detected within the first 15 min of the experiment (time of registering an AFM micrograph). Micrographs of functionalized glass with AuNPs covered with IC in the presence of water but with no irradiation at 0 h and at 5 h were taken as controls. There was no evidence of any difference in the micrographs or histograms between these time points. These results confirm that the variation in height of the particles was due only to the effect of plasmonic heating and rule out a possible degradation over time due to dissolution (Additional file 1: Figure S3 and S4).
In order to determine whether the laser increase the temperature in the experimental device, we determined this parameter in the water drop on the functionalized glass surface (with or without AuNPs) observing increments of about 4 °C after irradiation (Additional file 1: Figure S5). Notably, the local temperature around the AuNPs should reach 117 °C, which is consistent with thermal studies on solid IC that show reversible phase changes attributed to the movement of the guest molecule in CD cavities (Additional file 1: Figure S6). This finding is consistent with studies showing that it is possible to reach temperatures >100 °C via photothermal processes in liquid conditions .
To complement the AFM analysis, each stage of the glass functionalization was characterized by diffuse reflectance spectrophotometry.
In the absorption spectrum of the glass functionalized with AuNPs covered with IC,a bathochromic shift was again observed from the maximum of 530 to 542 nm, which is generated by a change in the immediate environment of the AuNPs conjugated to IC. Additionally, an asymmetrical broadening of the plasmonic band was observed, which is indicative of particles with a large size polydispersity due to an uneven deposition of IC over the surface of the AuNPs.
Finally, absorption spectrum of the irradiated sample was taken and showed a hypsochromic shift from 542 to 536 nm, which may be attributed to a partial release of IC from the surface of the AuNPs.
AFM and UV-Vis analyses demonstrated unequivocally the release of IC from the surface of the AuNPs when irradiated with a green laser.
Mass Spectrometry Analysis of the Water Drop After Irradiation
To elucidate whether the irradiation caused the disintegration of the IC, a mass spectrometry MALDI-TOF analysis was performed using a sample that contained a collection of drops obtained from the surface of functionalized glass slides previously irradiated for 20 min.
In this study, the functionalization of AuNPs glass slides was possible, and their overlay with IC was successful and was evaluated by AFM and UV-Vis spectrophotometry during every step of the glass assembly (activation, derivatization, functionalization, and coating of AuNPs with IC).
It was possible to confirm the release of ICs from the AuNPs surface, due to the plasmonic heat of the irradiated nanoparticles, by observing a decrease in the height of the AuNPs using AFM and by observing one hypsochromic shift of the plasmon band using UV-Vis spectrophotometry.
Analysis of the water drop on the surface of the irradiated glass using MALDI-TOF verified that the plasmonic heat led to the loss of the guest because the nominal mass corresponded only to α-CD and traces of OA.
This study provides the first evidence of the disintegration of an inclusion compound due to local heating of AuNPs by laser irradiation at a wavelength tunable with the plasmon, thus separating ICs from the AuNPs surface. By using other methodologies as NMR is difficult to set up the irradiation and the observation at the same time which could lead to the reversion of the process forming the IC and or the AuNP-IC system. The release of the guest molecule may be relevant in the field of drug delivery where spatial and temporal control of the release of a guest from an inclusion complex is desired. Moreover, we designed a methodology that could serve as a screening method to test the release of drugs based on the photothermal effect.
The authors acknowledged the financial support provide by the Fondecyt Project 1130147, 1130425, and Fondap 15130011. Scholarships Conicyt N.S. Gand AT-24121127, Beca de Pasantía Doctoral en el extranjero BECAS CHILE Convocatoria 2011. Prof. Samitier was funded by the project OLIGOCODES from the Spanish Ministry of Economy and Competitiveness MAT2012-38573-C02. The Nanobioengineering group has support from the Generalitat de Catalunya (2014 SGR 1442).
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