Gold nanohexapods represent a novel class of optically tunable nanostructures consisting of an octahedral core and six arms grown on its vertices. By controlling the length of the arms, their localized surface plasmon resonance peaks could be tuned from the visible to the near-infrared region for deep penetration of light into soft tissues. Herein we compare the in vitro and in vivo capabilities of Au nanohexapods as photothermal transducers for theranostic applications by benchmarking against those of Au nanorods and nanocages. While all these Au nanostructures could absorb and convert near-infrared light into heat, Au nanohexapods exhibited the highest cellular uptake and the lowest cytotoxicity in vitro for both the as-prepared and PEGylated nanostructures. In vivo pharmacokinetic studies showed that the PEGylated Au nanohexapods had significant blood circulation and tumor accumulation in a mouse breast cancer model. Following photothermal treatment, significant heat was produced in situ and the tumor metabolism was greatly reduced for all three gold nanostructures, as determined with 18F-flourodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Combined together, we can conclude that Au nanohexapods are promising candidates for cancer theranostics in terms of both photothermal destruction and contrast-enhanced diagnosis.
"Moreover, because of its easy use and minimal absorbance by skin and tissues, NIR radiation is also an attractive external stimulus to control the toxicity of the therapy through controlled release or enhanced therapeutic efficiency, thereby allowing noninvasive penetration of deep tissues2425262728. Conventional nanomaterial candidates featuring NIR imaging and photothermal properties are generally based on gold nanocages or nanorods1229303132. These materials have strong NIR absorbing capability and can efficiently convert NIR light into heat through photothermal processes. "
[Show abstract][Hide abstract] ABSTRACT: Using nanomaterials to develop multimodal systems has generated cutting-edge biomedical functions. Herein, we develop a simple chemical-vapor-deposition method to fabricate graphene-isolated-Au-nanocrystal (GIAN) nanostructures. A thin layer of graphene is precisely deposited on the surfaces of gold nanocrystals to enable unique capabilities. First, as surface-enhanced-Raman-scattering substrates, GIANs quench background fluorescence and reduce photocarbonization or photobleaching of analytes. Second, GIANs can be used for multimodal cell imaging by both Raman scattering and near-infrared (NIR) two-photon luminescence. Third, GIANs provide a platform for loading anticancer drugs such as doxorubicin (DOX) for therapy. Finally, their NIR absorption properties give GIANs photothermal therapeutic capability in combination with chemotherapy. Controlled release of DOX molecules from GIANs is achieved through NIR heating, significantly reducing the possibility of side effects in chemotherapy. The GIANs have high surface areas and stable thin shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications.
"Nanomaterial Laser wavelength Power intensity Irradiation time Cell line Reference Immuno Au nanocages 810 nm 4.7 W/cm 2 5 min SK-BR-3 (In vitro)  PEGylated Au nanocages 800 nm 1 W/cm 2 10 min U87MG with EGFR (In vivo)  Immuno Au nanocages 805 nm 1.6 W/cm 2 5 min SK-BR-3 (In vitro)  Au nanocages 808 nm 0.8 W/cm 2 10 min MDA-MB-435 (In vitro)  Au nanocages 750 nm 0.6 W/cm 2 10 min L929 (In vitro)  Au NR in-shell 808 nm 27 W/cm 2 8 min A549 (In vitro)  PEGylated Au nanoshells 808 nm 4 W/cm 2 3 min CT26.WT (In vitro)  Silica @ Au nanoshells 808 nm 30 W/cm 2 7 min A549 (In vitro)  Au nanoshell 820 nm 35 W/cm 2 7 min SK-BR-3 (In vitro)  Au NSemicelle 808 nm 8 W/cm 2 10 min HeLa (In vitro)  Lipid-coated Au nanocages 940 nm 0.056 W/cm 2 40 min HeLa (In vitro) Present study Lipid-coated Au nanocages 980 nm 0.15 W/cm 2 10 min B16F0 (In vivo) Present study R. Vankayala et al. / Biomaterials xxx (2014) 1e12 2 "
[Show abstract][Hide abstract] ABSTRACT: Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm(2)), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under ultra-low laser doses.
"In the case of gold nanoshells, there is a potential concern for the reason that the large shells are difficult to excrete from the body for extended periods of time 35. The use of cetyltrimethylammonium bromide (CTAB) in the synthesis of Au nanorods results in additional time and labor-consuming in the further purification and modification 36. In addition, the Au nanorods have weak stability under NIR irradiation since they are prone to melt and lose their efficiency 37, 38. "
[Show abstract][Hide abstract] ABSTRACT: Multifunctional nanostructures combining diagnosis and therapy modalities into one entity have drawn much attention in the biomedical applications. Herein, we report a simple and cost-effective method to synthesize a novel cubic Au nano-aggregates structure with edge-length of 80 nm (Au-80 CNAs), which display strong near-infrared (NIR) absorption, excellent water-solubility, good photothermal stability, and high biocompatibility. Under 808 nm laser irradiation for 5 min, the temperature of the solution containing Au-80 CNAs (100 μg/mL) increased by ~38 °C. The in vitro and in vivo studies demonstrated that Au-80 CNAs could act as both photothermal therapeutic (PTT) agents and photoacoustic imaging (PAI) contrast agents, indicating that the only one nano-entity of Au-80 CNAs shows great potentials for theranostic applications. Moreover, this facile and cost-effective synthetic method provides a new strategy to prepare stable Au nanomaterials with excellent optical properties for biomedical applications.
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