Detoxification of Gold Nanorods by Treatment with Polystyrenesulfonate

Abstract

We address an outstanding issue associated with the biocompatibility of gold nanorods (GNRs), a promising agent for biomedical imaging and theragnostics. GNRs are typically prepared in the presence of cetyltrimethylammonium bromide (CTAB), a cationic surfactant whose rigorous removal is necessary due to its cytotoxicity and membrane-compromising properties. CTABstabilized GNRs can be partially purified by treatment with polystyrenesulfonate (PSS), an anionic polyelectrolyte often used as a surrogate peptizing agent, followed by chloroform extraction and ultrafiltration with minimal loss of dispersion stability. However, in vitro cytotoxicity assays of PSScoated GNRs revealed IC 50 values in the low to submicromolar range, with subsequent studies indicating the source of toxicity to be associated with a persistent PSS-CTAB complex. Further exchange of CTAB-laden PSS with fresh polyelectrolyte greatly improves biocompatibility, to the extent that 85 μg/mL of "CTAB-free" GNRs (the highest level evaluated) has comparable toxicity to a standard phosphate buffer solution. Ironically, PSS is not effective by itself at stabilizing GNRs in CTAB-depleted suspensions: while useful as a detergent for GNR detoxification, it should be replaced by more robust coatings for long-term stability under physiological conditions. KeywordsNanorods; nanomedicine; nanobiotechnology; toxicity; dispersion stability Plasmon-resonant gold nanorods (GNRs) have attracted much recent attention for their potential as multifunctional agents in theragnostics, an integrated approach to diagnostic imaging and therapy. 1,2,3 GNRs are well known for their very high extinction coefficients at near-infrared (NIR) wavelengths; when excited at plasmon resonance, they can serve simultaneously as optical contrast agents and as photothermal transducers capable of mediating local heating effects. 4,5,6,7,8,9 These resonances are tunable as a function of size and shape: the absorption and scattering cross sections both increase rapidly with particle volume, whereas the plasmon frequencies are sensitive to particle anisotropy and aspect ratio. For in vivo applications, nanoparticles with NIR resonances are particularly favored because of the relatively high transmittivity of biological tissues in the spectral range between 750 and 1300 nm. Other examples of NIR-absorbing Au nanoparticles used in theragnostic applications include nanoshells, 10,11 nanocages, 12 and aggregates of spherical nanoparticles. 13,14 In order to be considered for translation to clinical studies, nanoparticles and their functionalized derivatives must pass a preclinical evaluation commonly referred to as adsorption, distribution, metabolism, excretion and toxicity (ADMET) profiling. These are performed in vivo using standard animal models, but are usually preceded by in vitro cell-based assays for preliminary evaluation of selective targeting and cytotoxicity. Cell-based assays provide a rapid and cost-effective method for evaluating three practical issues that affect the viabil...

Engineering Gold Nanotubes with Controlled Length and Near‐Infrared Absorption for Theranostic Applications

“…The positively charged CTAB-Au NTs were coated with negatively charged sodium polystyrenesulfonate (PSS, 70 kDa) (see Experimental Section), which is commonly used as a nontoxic peptizing agent in commercial products and thus generally regarded as a safe additive. [42] After the treatment with PSS, a thin organic layer around the nanotubes was observed in TEM image ( Figure S8A), which is a direct visualization of polymer coating of the Au NTs. [43] The Zeta potential of gold nanotubes (in DI water) changed from (45±3.…”

SERS Tags: Novel Optical Nanoprobes for Bioanalysis

“…However, when CTAB was replaced with PEG-SH, 95% of cells were viable, with the Au NRs concentration being 0.5 mM. Further works demonstrated that the replacement or overcoating of CTAB with nontoxic stabilizers of PSS, 305 PAH, 306 or copolymer poly-(diallyldimethylammonium chloride)/polystyrene sulfonic acid 307 reduced the cytotoxicity of CTAB-stabilized Au NRs. Surface charge also affects the toxicity of noble metal NPs.…”

Echographic detectability of optoacoustic signals from low-concentration PEG-coated gold nanorods

“…These highly biocompatible ligands replace the CTAB molecules originally covering the surface of the as-synthesized NRs, which instead are known to be highly toxic. 43,44 Successful PEGylation of GNRs was verified through zeta-potential measurements of the GNRs in water before and after the ligand-exchange procedure, as described in the next section.…”