Gemini Imidazolium Amphiphiles for the Synthesis, Stabilization, and Drug Delivery from Gold Nanoparticles

Abstract

Gold nanoparticles (AuNPs) are considered useful vehicles for medical therapy and diagnosis. Despite the progress made in this field, there is need to find direct, reliable, and versatile synthetic procedures for their preparation as well as new multifunctional coating agents. In this sense, we have explored the use of imidazolium amphiphiles to prepare new AuNPs designed for anion recognition and transport. Thus, in this work we describe (a) the synthesis, by a phase transfer method, of new gold nanoparticles using gemini-type surfactants as ligands based on imidazolium salts, those ligands acting as transfer agents into organic media and also as nanoparticle stabilizers, (b) the examination of their stability in solution, (c) the chemical and physical characterization of the nanoparticles, using a variety of techniques, including UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), (d) toxicity data concerning both the imidazolium ligands and the imidazolium coated nanoparticles, (e) the assessment of their molecular recognition ability toward molecules of biological interest, such as anions and carboxylate containing model drugs, such as ibuprofen, (f) the study of their toxicity and those of their coating ligands, as well as their ability for cell internalization, and (g) the study of their ability for delivering anionic pharmaceuticals. The structurally governed triple role of those new gemini-type surfactants is responsible for the preparation, remarkable stability, and delivery properties of these functional AuNPs.

Gemini pyridinium amphiphiles for the synthesis and stabilization of gold nanoparticles for drug delivery

“…This density is similar to the previously reported AuNPs incorporating gemini imidazolium amphiphiles as stabilizer agents. [22,25] Overall, it seems to confirm that the minority ligand 1·2Br forms a layer around the gold core, so that the formed 2·AuNPs have the positively charged pyridinium heads layer favouring stabilization of the gold core, and the tetrahydropyridine 2 forms a layer around the bispyridinium salt 1·2Br. This particular disposition would explain why 1·2Br could not be noticeably detected by MALDI-ToF MS and 1 H NMR spectroscopy.…”

“…Remarkably, 2'·AuNPs were found to be stable and monodisperse only when synthesized in the presence of KBr, indicating not only how crucial are the long chains in the amphiphile but the critical role of anions in their structure for the synthesis and stability of these nanoparticles, as described in previous report. [22,33] The close proximity of the ligand 1·2Br to the metallic core was confirmed by different techniques such as MALDI-ToF MS and NMR spectroscopy. The ligand 1·2Br as well as 2·AuNPs and 3·AuNPs were neither cytotoxic nor genotoxic to the cell lines studied (3T3/NIH, HepG2 and CaCo-2) at the concentrations tested, when compared with similar structures using the same cell lines.…”

“…The spectra were recorded using DHB as the matrix. Despite precedents from the literature reports, [22,23,25] on bis-imidazolium coated nanoparticles, the experimental conditions for recording sufficiently informative spectra were difficult to find. As we can see in Table 3 and Table S3 see Supplementary Material, all nanoparticles but 1·AuNPs have multicomponent coatings.…”

“…[22,23] These molecules show anion binding properties in solution, and therefore they play a unique triple role, acting as phase transfer agent of the gold salt during the synthesis, capping agent for the stabilization of the AuNPs, and binding agent for anionic molecules, resulting in a major simplification of the synthetic process and subsequent purification of the functional nanomaterial. [22] Furthermore, the ability of bis-imidazolium salts to complex anions, [24] particularly carboxylates, allowed the incorporation and delivery of a carboxylate-containing model drug. [22,25] As a step forward in this research we have focused on the use of gemini amphiphiles based on bispyridinium salts in the synthesis of AuNPs, expecting that these molecules would expand the anion recognition ability of the nanomaterials.…”

“…[22] Furthermore, the ability of bis-imidazolium salts to complex anions, [24] particularly carboxylates, allowed the incorporation and delivery of a carboxylate-containing model drug. [22,25] As a step forward in this research we have focused on the use of gemini amphiphiles based on bispyridinium salts in the synthesis of AuNPs, expecting that these molecules would expand the anion recognition ability of the nanomaterials. To test the AuNPs' ability to incorporate and release anionic molecules, two model drugs were used: ibuprofen and piroxicam, which are non-steroidal anti-inflammatory drugs widely used in inflammatory arthritis and osteoarthritis.…”