Development of chitosan oligosaccharide-modified gold nanorods for in vivo targeted delivery and noninvasive imaging by NIR irradiation.

In the present study, we demonstrate the synthesis and applications of multifunctional gold nanorod-based probes for specific targeting and noninvasive imaging based on localized heating generated by gold nanorods after NIR irradiation. The structural design of the probe consists of MUA (11-mercaptoundecanoic acid)-capped gold nanorods covalently linked with low-molecular-weight chitosan oligosaccharide (M(w) ~5000) via carbodiimide (EDC) coupling agent. This surface modification is performed for complete replacement of toxic CTAB (hexadecyltrimethyl-ammonium chloride) and acid-responsive delivery of gold nanorods in acidic environment as known to be present at tumor surrounding areas. The resulting chitosan oligosaccharide-modified gold nanorods (CO-GNRs) were further conjugated with tumor targeting monoclonal antibody against EGFR (epidermal growth factor receptor) to provide localized targeting functionality owing to the overexpression of EGFR in human oral adenosquamous carcinoma cell line CAL 27. Initial in vitro and in vivo toxicity assessments indicated that CO-GNRs did not induce any significant toxicity and are thus suitable for biological applications. Furthermore, selective targeting and accumulation of CO-GNRs were observed in vitro via two-photon luminescence imaging studies in CAL 27, which was also observed through in vivo targeting studies performed via NIR (near-infrared) laser irradiation in CAL 27 xenografts of BALB/c nude mice. Hence, the CO-GNRs that we have developed are biocompatible and nontoxic and can be a potential candidate for in vivo targeted delivery, noninvasive imaging based on localized hyperthermia, and photothermal-related therapies.

Synthesis of tunable and multifunctional Ni-doped near-infrared QDs for cancer cell targeting and cellular sorting.

Here, we report the facile preparation of tunable magnetic Ni-doped near-infrared (NIR) quantum dots (MNIR-QDs) as an efficient probe for targeting, imaging, and cellular sorting applications. We synthesized the MNIR-QDs via a hot colloidal synthesis approach to yield monodisperse and tunable QDs. These hydrophobic QDs were structurally and compositionally characterized and further functionalized with amino-PEG and carboxyl-PEG to improve their biocompatibility. Since QDs are known to be toxic due to the presence of cadmium, we have evaluated the in vitro and in vivo toxicity of our surface-functionalized MNIR-QDs. Our results revealed that surface-functionalized MNIR-QDs did not exhibit significant toxicity at the concentrations used in the experiments and are therefore suitable for biological applications. For further in vitro applications, we covalently linked folic acid to the surface of amino-PEG-coated MNIR-QDs through NHS chemistry to target the folate receptors largely present in the HeLa cells to demonstrate the specific targeting and magnetic behavior of these MNIR-QDs. Improved specificity has been observed with treatment of HeLa cells with the folic acid-linked amino PEG-coated MNIR QDs (FA-PEG-MNIR-QDs) compared to the one without folic acid. Since the synthesized probe has magnetic property, we have also successfully demonstrated sorting between the cells which have taken up the probe with the use of a magnet. Our findings strongly suggest that these functionalized MNIR-QDs can be a potential probe for targeting, cellular sorting, and bioimaging applications.

Development of lipid targeting Raman probes for in vivo imaging of Caenorhabditis elegans.

A simple, sensitive, and highly specific lipid targeting Raman probe (Nile red coated silver nanoparticles) has been developed to image living nematode Caenorhabditis elegans (C. elegans). Our idea of imaging lipids in C. elegans is to combine the specificity of the fluorescent dye, Nile red, and the highly enhanced Raman scattering on the silver nanoparticles. Our strategy involves the fabrication of a lipid targeting probe, which is incorporated into the intracellular intestinal granules of C. elegans by incubating these worms in the solution containing Raman probes, resulting in an uptake and subsequent incorporation of these Raman probes into the intestinal granule, thus allowing fast visualization of lipid droplets through a conventional confocal imaging technique.

Direct synthesis of nanocrystalline silver from the reaction between silver carboxylates and n-trioctylphosphine.

Neat n-Trioctylphosphine (TOP) has been used for the first ever time for reduction of silver nitrate and silver carboxylates (citrate, oleate, and myristate) under mild thermal reaction conditions. UV-visible absorption measurements of re-dispersible silver particles that were obtained by reduction of silver myristrate (product-IV) and silver nitrate (product-I) showed surface plasmon resonance absorption peak at 400 nm. The powder XRD pattern of fcc zero-valent silver resulted in diameters in the range of about 25-30 nm. TEM analysis showed particle diameter similar to that was observed by the XRD. FTIR spectroscopy revealed that the organics from the carboxylate group are retained by the nano-particles in case of product-IV however, presence of TOP is observed in product-I. It is found that when silver nitrate is reduced by TOP, spherical silver nano-particles with poor redispersity are formed but extended heating results in formation of long silver rods of micrometer size however, the re-dispersible nano-particles are easily formed when silver carboxylates are reduced by TOP.