Gold nanorods carrying paclitaxel for photothermal-chemotherapy of cancer.

Nanotechnology-based photothermal therapy has emerged as a promising treatment for cancer during the past decade. However, heterogeneous laser heating and limited light penetration can lead to incomplete tumor cell eradication. Here, we developed a method to overcome these limitations by combining chemotherapy with photothermal therapy using paclitaxel-loaded gold nanorods. Paclitaxel was loaded to gold nanorods with high density (2.0 × 10(4) paclitaxel per gold nanorod) via nonspecific adsorption, followed by stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. Paclitaxel was entrapped in the hydrophobic pocket of the polymeric monolayer on the surface of gold nanorods, which allows direct cellular delivery of the hydrophobic drugs via the lipophilic plasma membrane. Highly efficient drug release was demonstrated in a cell membrane mimicking two-phase solution. Combined photothermal therapy and chemotherapy with the paclitaxel-loaded gold nanorods was shown to be highly effective in killing head and neck cancer cells and lung cancer cells, superior to photothermal therapy or chemotherapy alone due to a synergistic effect. The paclitaxel-gold nanorod enabled photothermal chemotherapy has the potential of preventing tumor reoccurrence and metastasis and may have an important impact on the treatment of head and neck cancer and other malignancies in the clinic.

Photosensitizer-loaded gold nanorods for near infrared photodynamic and photothermal cancer therapy.

Despite the advancement of photodynamic therapy and photothermal therapy, the ability to form compact nanocomplex for combined photodynamic and photothermal cancer therapy under a single near infrared irradiation remains limited. In this work, we prepared an integrated sub-100 nm nanosystem for simultaneous near infrared photodynamic and photothermal cancer therapy. The nanosystem was formed by adsorption of silicon 2,3-naphthalocyanine dihydroxide onto gold nanorod followed by covalent stabilization with alkylthiol linked polyethylene glycol. The effects of alkylthiol chain length on drug loading, release and cell killing efficacy were examined using 6-mercaptohexanoic acid, 11-mercaptoundecanoic acid and 16-mercaptohexadecanoic acid. We found that the loading efficiency of silicon 2,3-naphthalocyanine dihydroxide increased and the release rate decreased with the increase of the alkylthiol chain length. We demonstrated that the combined near infrared photodynamic and photothermal therapy using the silicon 2,3-naphthalocyanine dihydroxide-loaded gold nanorods exhibit superior efficacy in cancer cell destruction as compared to photodynamic therapy and photothermal therapy alone. The nanocomplex stabilized with 16-mercaptohexadecanoic acid linked polyethylene glycol provided highest cell killing efficiency as compared to those stabilized with the other two stabilizers under low drug dose. This new nanosystem has potential to completely eradicate tumors via noninvasive phototherapy, preventing tumor reoccurrence and metastasis.

Size- and Shape-Controlled Synthesis and Properties of Magnetic-Plasmonic Core-Shell Nanoparticles.

Magnetic-plasmonic core-shell nanomaterials offer a wide range of applications across science, engineering and biomedical disciplines. However, the ability to synthesize and understand magnetic-plasmonic core-shell nanoparticles with tunable sizes and shapes remains very limited. This work reports experimental and computational studies on the synthesis and properties of iron oxide-gold core-shell nanoparticles of three different shapes (sphere, popcorn and star) with controllable sizes (70 to 250 nm). The nanoparticles were synthesized via a seed-mediated growth method in which newly formed gold atoms were added onto gold-seeded iron oxide octahedrons to form gold shell. The evolution of the shell into different shapes was found to occur after the coalescence of gold seeds, which was achieved by controlling the amount of additive (silver nitrate) and reducing agent (ascorbic acid) in the growth solution. First principles calculation, together with experimental results, elucidated the intimate roles of thermodynamic and kinetic parameters in the shape-controlled synthesis. Both discrete dipole approximation calculation and experimental results showed that the nanopopcorns and nanostars exhibited red-shifted plasmon resonance compared with the nanospheres, with the nanostars giving multispectral feature. This research has made a great step further in manipulating and understanding magnetic-plasmonic hybrid nanostructures and will make important impact in many different fields.

Nanotechnology for enrichment and detection of circulating tumor cells.

Circulating tumor cells (CTCs) are a hallmark of invasive behavior of cancer, responsible for the development of metastasis. Their detection and analysis have significant impacts in cancer biology and clinical practice. However, CTCs are rare events and contain heterogeneous subpopulations, requiring highly sensitive and specific techniques to identify and capture CTCs with high efficiency. Nanotechnology shows strong promises for CTC enrichment and detection owning to the unique structural and functional properties of nanoscale materials. In this review, we discuss the CTC enrichment and detection technologies based on a variety of functional nanosystems and nanostructured substrates, with the goal to highlight the role of nanotechnology in the advancement of basic and clinical CTC research.

Near-infrared-absorbing gold nanopopcorns with iron oxide cluster core for magnetically amplified photothermal and photodynamic cancer therapy.

We present the synthesis and application of a new type of dual magnetic and plasmonic nanostructures for magnetic-field-guided drug delivery and combined photothermal and photodynamic cancer therapy. Near-infrared-absorbing gold nanopopcorns containing a self-assembled iron oxide cluster core were prepared via a seed-mediated growth method. The hybrid nanostructures are superparamagnetic and show great photothermal conversion efficiency (η=61%) under near-infrared irradiation. Compact and stable nanocomplexes for photothermal-photodynamic therapy were formed by coating the nanoparticles with near-infrared-absorbing photosensitizer silicon 2,3-naphthalocyannie dihydroxide and stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. The nanocomplex showed enhanced release and cellular uptake of the photosensitizer with the use of a gradient magnetic field. In vitro studies using two different cell lines showed that the dual mode photothermal and photodynamic therapy with the assistance of magnetic-field-guided drug delivery dramatically improved the therapeutic efficacy of cancer cells as compared to the combination treatment without using a magnetic field and the two treatments alone. The "three-in-one" nanocomplex has the potential to carry therapeutic agents deep into a tumor through magnetic manipulation and to completely eradicate tumors by subsequent photothermal and photodynamic therapies without systemic toxicity.

Integration of a nanostructured dielectrophoretic device and a surface-enhanced Raman probe for highly sensitive rapid bacteria detection.

This work reports a synergistic approach to the concentration, detection and kinetic monitoring of pathogens through the integration of nanostructured dielectrophoresis (DEP) with nanotag-labelled Surface Enhanced Raman Spectroscopy (SERS). A nanoelectrode array made of embedded Vertically Aligned Carbon Nanofibers (VACNFs) at the bottom of a microfluidic chip was used to effectively capture and concentrate nanotag-labelled E. coli DHα5 cells into a 200 µm × 200 µm area on which a Raman laser probe was focused. The SERS nanotags were based on iron oxide-gold (IO-Au) core-shell nanoovals (NOVs) of ∼50 nm size, which were coated with a QSY21 Raman reporter and attached to E. coli through specific immunochemistry. The combination of the greatly enhanced Raman signal by the SERS nanotags and the effective DEP concentration significantly improved the detection limit and speed. The SERS signal was measured with both a confocal Raman microscope and a portable Raman probe during DEP capture, and was fully validated with fluorescence microscopy measurements under all DEP conditions. The SERS measurements were sensitive enough to detect a single bacterium. A concentration detection limit as low as 210 cfu ml(-1) using a portable Raman system was obtained with a DEP capture time of only ∼50 s. These results demonstrate the potential to develop a compact portable system for rapid and highly sensitive detection of specific pathogens. This system is reusable, requires minimum sample preparation, and is amenable to field applications.

Capture and detection of cancer cells in whole blood with magnetic-optical nanoovals.

AIM: To develop a simple assay for the capture and detection of rare cancer cells in whole blood using iron oxide-gold (IO-Au) nanoparticles. MATERIALS & METHODS: IO-Au nanoovals (NOVs) were synthesized, coated with Raman tags and linked with antibodies targeting breast cancer. An integrated system was constructed for on-line magnetic cell capture and surface-enhanced Raman scattering (SERS) detection. The capabilities of IO-Au SERS NOVs to capture and detect rare cancer cells in blood were investigated in the integrated system using circulating tumor cell-mimic SK-BR-3 cells. RESULTS: SK-BR-3 cells in whole blood were magnetically captured under a flow condition using IO-Au SERS NOVs, followed by on-line SERS detection with a limit of detection of 1-2 cells/ml blood. CONCLUSION: We developed a sensitive method that can capture and detect cancer cells in whole blood with a single nanoconstruct, which is highly promising for the detection of circulating tumor cells in the clinic.

Impact of core dielectric properties on the localized surface plasmonic spectra of gold-coated magnetic core-shell nanoparticles.

Gold-coated iron oxide core-shell nanoparticles (IO-Au NPs) are of interest for use in numerous biomedical applications because of their unique combined magnetic-plasmonic properties. Although the effects of the core-dielectric constant on the localized surface plasmon resonance (LSPR) peak position of Au-shell particles have been previously investigated, the impact that light-absorbing core materials with complex dielectric functions have on the LSPR peak is not well established. In this study, we use extended Mie theory for multilayer particles to examine the individual effects of the real and imaginary components of core refractive indices on Au-shell NP plasmonic peaks. We find that the imaginary component dampens the intensity of the cavity plasmon and results in a decrease of surface plasmon coupling. For core materials with large imaginary refractive indices, the coupled mode LSPR peak disappears, and only the anticoupled mode remains. Our findings show that the addition of a nonabsorbing polymer layer to the core surface decreases the dampening of the cavity plasmon and increases LSPR spectral intensity. Additionally, we address apparent discrepancies in the literature regarding the effects of Au-shell thickness on LSPR peak shifts.

Synthesis and properties of near infrared-absorbing magnetic-optical nanopins.

Novel near infrared-absorbing iron oxide-gold core-shell nanoparticles in pin shapes were synthesized. The nanopins are superparamagnetic, with 35-fold better surface enhanced Raman scattering activities than the conventional core-shell nanospheres and 50-fold greater photothermal properties than solid gold nanorods. The nanoparticles will have important impact on medical imaging, molecular diagnostics and disease treatment.