Halide-Gated Molecular Release from Nanoporous Gold Thin Films

Abstract

Nanoporous materials have attracted significant attention as drug delivery platforms, in which interfacial phenomena are often more influential than fluid mechanics in defining molecular loading capacity and release kinetics. This study employs nanoporous gold (np-Au) as a model material system to investigate physical mechanisms of molecular release of fluorescein (a small molecule drug surrogate) from the sub-micron-thick np-Au coatings. Specifically, the study reveals an interfacial mechanism where halide ion-gold surface interactions dictate the loading capacity and release kinetics of fluorescein. We systematically study the effect of halide concentration and species on release kinetics from sputter-deposited np-Au films with a combination of quantitative electron microscopy, fluorospectrometry, and electrochemical surface characterization techniques. The results suggest that the interplay of halide-gold interaction probability and affinity determine the nature of release kinetics. The former mechanism plays a more dominant role at higher ionic strengths, while the latter is more important at lower ionic strengths. This interfacial phenomenon is further complemented by functionalizing the np-Au with self-assembled monolayers (SAMs) of alkane-thiols for modulating gold surface-halide affinity and consequently the molecular release kinetics.

Effect of Surface–Molecule Interactions on Molecular Loading Capacity of Nanoporous Gold Thin Films

“…Via the similar electrostatic interaction based mechanism, the amine-modified np-Au displayed high loading capacity (0.6 μg/cm 2 ) due to the positively-charged surface, indicating that the loading capacity can be drastically changed by controlling the surface-molecule interactions by tailoring surface properties via SAM immobilization. The loading capacity for the amine-modified np-Au was approximately two-fold less than non-modified np-Au, which can be attributed to the reduction in the number of sites available for fluorescein adsorption for the SAM case (amine groups separated due to electrostatic repulsion 21 ) in comparison to non-modified gold (densely packed gold lattice) 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 9 (calculated by Stokes-Einstein equation) 11 . On the other hand, packing density of alkanethiolates with comparable size and charge (consequently the functional group density for fluorescein adsorption) on Au (111) is approximately 5 molecules/nm 2 based on theoretical calculations 22 .…”

“…Our previous work describes the detailed fabrication of patterned np-Au thin films used in the release experiments 11,16 . Briefly, in order to fabricate the release chips (also referred to as release samples) used for molecular release from 3 mm x 3 mm np-Au patterns, we sputtered a stack of metal layers through a laser-cut PDMS stencil mask temporarily placed on glass coverslips.…”

“…To that end, we used 100 mM CaCl2 as the loading medium and PBS was selected as the elution medium. It 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 should be noted that halide ions results in a fast release of fluorescein from non-modified np-Au films by substituting adsorbed fluorescein molecules due to high gold-halide affinity 16 . In order to control the possible influence of chloride in this experiment and to decouple calcium ions' effect on loading capacity, 100 mM Ca(NO3)2 was used for the loading medium as a control group.…”

“…Nanoporous gold (np-Au), with its high effective surface area, well established gold-thiol-mediated surface modifications, and tunable pore morphology, is a promising material for drug delivery applications and studying the influence of physicochemical surface properties on the moleculeloading capacity and release kinetics [8][9][10][11][12][13][14][15] . Our previous studies have focused on the effect of pore morphology and elution medium constituents on the molecular release from np-Au coatings 11,16 . These studies highlighted the significance of surface-molecule interactions in dictating molecular release from np-Au.…”

Electrochemical impedance spectroscopy study of carbohydrate-terminated alkanethiol monolayers on nanoporous gold: Implications for pore wetting

“…These applications typically involve prior modification of the np-Au with SAMs with various terminal functional groups, and are often followed by covalent immobilization of biomolecules to the np-Au surfaces; however, accessibility is also important for cases of modification by simple physical adsorption. Accessibility of electrolyte solutions to the interior of np-Au can be viewed as significant for the efficiency of immobilization of biomolecules such as antibodies [31–33] or oligonucleotides [25, 34], sensor response [1], loading for controlled release [10, 35], and substrate access and overall activity for immobilized enzymes [36]. Carbohydrate modified np-Au has been recently explored for applications in capture and elution of lectins [21], glycoprotein modified np-Au for competitive electrochemical immunoassay, and lectin-modified np-Au for capture and subsequent elution of glycoproteins [22].…”