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...

Plasmon-resonant nanoparticles with optical scattering in the near infrared (NIR) are valuable contrast agents for biophotonic imaging and may be detected at the single-particle limit against a dark background, but their contrast is often limited in environments with high noise. Here we consider gyromagnetic imaging as a dynamic mode of optical contrast, using gold nanostars with superparamagnetic cores. The nanostars exhibit polarization-sensitive NIR scattering, and can produce a frequency-modulated signal in response to a rotating magnetic field gradient. This periodic "twinkling" can be converted into Fourier-domain images with a dramatic reduction in background. We demonstrate gyromagnetic imaging of nanostars inside of tumor cells, using broadband excitation: while their time-domain signals are obscured by incoherent scattering, their Fourierdomain signals can be clearly resolved in less than a second. The gyromagnetically active nanostars do not cause a loss in viability, and can even have a mild stimulatory effect on cell growth.

A chitosan derivative was prepared with good yields using a "one pot" approach by grafting L-lactide oligomers via ring opening polymerization. Side chains are primarily attached to hydroxyl groups located on carbons 3 and 6 of the glucosamine ring, while the amine group remains nonfunctionalized. By increasing the L-lactide to chitosan ratio, side chain length is controlled. This allows the manipulation of the biodegradation rate and hydrophilicity of the tissue engineering scaffold material. This general synthetic route renders functionalized chitosan soluble in a broad range of organic solvents, facilitating formation of ultrafine fibers via electrospinning. Cytotoxicity tests using fibroblasts (L929 cell line) performed on electrospun L-lactide modified chitosan fibers showed that the specimen with the highest molar ratio of L-lactide (1:24) investigated in this study is the most promising material for tissue engineering purposes, while less stable formulations might still find application in drug delivery vehicles.

Bishydrazides are versatile linkers for attaching glycans to substrates for lectin binding and pathogen detection schemes. The α,ω-bishydrazides of carboxymethylated hexaethylene glycol (4) can be conjugated at one end to unprotected oligosaccharides, then attached onto carrier proteins, tethered onto activated carboxyl-terminated surfaces, or functionalized with a photoactive crosslinking agent for lithographic patterning. Glycoconjugates of bishydrazide 4 can also be converted into dithiocarbamates (DTCs) by treatment with CS 2 under mild conditions, for attachment onto gold substrates. The immobilized glycans serve as recognition elements for cellsurface lectins and enable the detection and capture of bacterial pathogens such as Psuedomonas aeruginosa by their adsorption onto micropatterned substrates. A detection limit of 10 3 cfu/mL is demonstrated, using a recently introduced method based on optical pattern recognition.