Search

Background: Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations., Main Body: In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold-thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA., Conclusion: We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.

Highly sensitive and reproducible surface enhanced Raman spectroscopy (SERS) requires not only a nanometer-level structural control, but also superb uniformity across the SERS substrate for practical imaging and sensing applications. However, in the past, increased reproducibility of the SERS signal was incompatible with increased SERS sensitivity. This work presents multiple silver nanocrystals inside periodically arrayed gold nanobowls (SGBs) via an electrochemical reaction at an overpotential of -3.0 V (vs. Ag/AgCl). The gaps between the silver nanocrystals serve as hot spots for SERS enhancement, and the evenly distributed gold nanobowls lead to a high device-to-device signal uniformity. The SGBs on the large sample surface exhibit an excellent SERS enhancement factor of up to 4.80 × 10 9 , with excellent signal uniformity (RSD < 8.0 ± 2.5%). Furthermore, the SGBs can detect specific microRNA (miR-34a), which plays a widely acknowledged role as biomarkers in diagnosis and treatment of diseases. Although the small size and low abundance of miR-34a in total RNA samples hinder their detection, by utilizing the advantages of SGBs in SERS sensing, reliable and direct detection of human gastric cancer cells has been successfully accomplished.

Various types of nanoprobes have recently been utilized to monitor living organisms by detecting and imaging intracellular biomarkers, such as microRNAs (miRs). We here present a simple one-pot method to prepare stellate gold nanoparticles functionalized with miR-detecting molecular beacons (SGNP-MBs); low pH conditions permitted the rapid-high loading of MBs on the surface of SGNPs. Compared to the conventional gold nanoparticle-based MBs, SGNPs carried a 4.5-fold higher load of MBs and exhibited a 6.4-fold higher cellular uptake. We demonstrated that SGNP-MBs were successfully internalized in human gastric cancer cell lines and could be used to accurately detect and image intracellular miRs in an miR-specific manner. Furthermore, the relative levels of intracellular miRs in three different cell lines expressing miR-10b (high, moderate, and low levels) could be monitored using SGNP-MBs. Consequently, these results indicated that SGNP-MBs could have applications as highly potent, efficient nanoprobes to assess intracellular miR levels in living cells.

Silica-gold nanoshell (SGNS), which is a silica core surrounded by a gold layer, was synthesized by seed-mediated coalescence of gold clusters in an electroless plating solution. SGNS variations with different surface coverage of gold clusters were prepared by adjusting the amounts of gold salts in the presence of formaldehyde-reducing agents. Fully covered SGNS (f-SGNS) with connected gold clusters exhibited stronger intensity and more redshift of plasmon bands located around 820 nm than those of partially covered SGNS (p-SGNS) with disconnected gold clusters. Upon irradiation with near-infrared light (30 W/cm(2), 700-800 nm), f-SGNS caused a larger hyperthermia effect, generating a large temperature change (ΔT =42°C), as compared to the relatively small temperature change (ΔT =24°C) caused by p-SGNS. The therapeutic antibody, Erbitux™ (ERB), was further conjugated to SGNS for specific tumor cell targeting. The f-ERB-SGNS showed excellent therapeutic efficacy based on the combined effect of both the therapeutic antibody and the full hyperthermia dose under near-infrared irradiation. Thus, SGNS with well-controlled surface morphology of gold shells may be applicable for near-infrared-induced hyperthermia therapy with tunable optical properties.

Here, wire-framed Au nanobundles (WNBs), which consist of randomly oriented and mutually connected Au wires to form a bundle shape, are synthesized. In contrast to conventional nanoparticles (spheres, rods, cubes, and stars), which exhibit nanostructure only on the surface, cross-sectional view image shows that WNBs have nanostructures in a whole volume. By using this specific property of WNBs, an externally controllable multistep photothermic-driven drug release (PDR) system is demonstrated for in vivo cancer treatment. In contrast to conventional nanoparticles that encapsulate a drug on their surface, WNBs preserve the drug payload in the overall inner volume, providing a drug loading capacity sufficient for cancer therapy. An improved in vivo therapeutic efficacy of PDR therapy is also demonstrated by delivering sufficient amount of drugs to the target tumor region., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We describe the development of biomarker-sensitive nanoprobes based on nanoparticle surface energy transfer (NSET) effect that enabling recognition of the expression of membrane type-1 matrix metalloproteinase (MT1-MMP) anchored on invasive cancer cells and its proteolytic activity simultaneously. First of all, we confirmed invasiveness of cancer cell lines (HT1080 and MCF7) via migration and invasion assay. We also prepared gold nanoparticle (GNP) acts as a quencher for fluorescein isothiocyanate (FITC). This FITC is conjugated in end-terminal of activatable fluorogenic peptide (ActFP). The ActFP attach to surface of GNP (GNP-ActFP) for a targeting moiety and proteolytic activity ligand toward MT1-MMP. The GNP-ActFP can generate fluorescence signal when ActFP is cleaved by proteolytic activity after targeting toward MT1-MMP. In order to study specificity for MT1-MMP, GNP-ActFP is treated to HT1080 and MCF7 cells, and then, we determine the in vitro targeting potential and fluorogenic activity of GNP-ActFP for MT1-MMP via fluorescence multi-reader. We also confirmed fluorogenic activity of GNP-ActFP via confocal microscopic imaging, and finally, endocytosis of GNP-ActFP is observed via cellular transmission electron microscopic imaging., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Biomarker-specific photothermal nanoparticles that can efficiently sense markers that are overexpressed in distinguished adenocarcinomas have attracted much interest in an aspect of efficacy increase of cancer treatment. We demonstrated a promising prospect of a smart photothermal therapy agent employing anti-epidermal growth factor receptor aptamer (AptEGFR)-conjugated polyethylene glycol (PEG) layted gold nanorods (AptEGFR-PGNRs). The cetyltrimethylammonium bromide bilayer on GNRs was replaced with heterobifunctional PEG (COOH-PEG-SH) not only to serve as a biocompatible stabilizer and but also to conjugate AptEGFR. Subsequently, to direct photothermal therapy agent toward epithelial cancer cells, the carboxylated PEGylated GNRs (PGNRs) were further functionalized with AptEGFR using carbodiimide chemistry. Then, to assess the potential as biomarker-specific photothermal therapy agent of synthesized AptEGFR-PGNRs, the optical properties, biocompatibility, colloidal stability, binding affinity, and epicellial cancer cell killing efficacy in vitro/in vivo under near-infrared laser irradiation were investigated. As a result, AptEGFR-PGNRs exhibit excellent tumor targeting ability and feasibility of effective photothermal ablation cancer therapy.

Heterogeneous stem-like populations within tumor tissues are the primary suspects in causing cancer recurrence and malignancy. It is essential to selectively kill these tumorigenic populations. We created a novel system for photothermally ablating specific cells from three-dimensional mammospheres. A CD44-positive subpopulation, with tumorigenic and self-renewal potential, spontaneously arises in MCF7 breast cancer cell-engineered mammospheres. Using anti-CD44 antibody-linked gold nanorods, which strongly absorb near infrared light and increase local temperature, we effectively targeted and photo-ablated atypical cells. This biomarker-specific photothermal ablation model, using a smart nanoplatform, is a promising new strategy for selectively killing cancer cells, while sparing normal tissues.

Well-designed photothermal nanostructures have attracted many scientists pursuing a better means to accurately diagnose cancer and assess the efficacy of treatment. Recently, gold-based nanostructures (nanoshells, nanorods and nanocages) have enabled photothermal ablation of cancer cells with near-infrared (NIR) light without damaging normal human tissues and in particular, animal studies and early clinical testing showed the great promise for these materials. In this review article, we first discuss the mechanism of the cellular death signaling by thermal stress and introduce the intrinsic properties of gold nanostructures as photothermal agent for cancer treatment. Then the overview follows for evolving researches for the synthesis of various types of gold nanostructures and for their biomedical applications. Finally we introduce the optimized therapeutic strategies involving nanoparticle surface modification and laser operation method for an enhanced accumulation of gold nanostructures to the target cancer as well as for an effective cancer cell ablation.

Thiolated dextran-coated gold nanorods (DEX-GNRs) were synthesized for targeted delivery to inflammatory macrophages and their photothermal ablation under near-infrared (NIR) light irradiation. Successful synthesis of DEX-GNRs was achieved using thiolated dextran, generated by applying mercaptopropionic acid to transform a hydroxyl group of dextran into a thiol group which has strong binding affinity with surfaces of GNRs. We confirmed both the existence of a thiol group in the functionalized dextran using Ellman's reagent in a thiol group assay and the characteristic band of DEX-GNRs using FT-IR spectrum. Furthermore, a cellular uptake study revealed that dextran showed a superior ability to bind the GNRs surface against macrophages compared to those of PEGylated GNRs with various molecular weights of polyethyleneglycol (PEG). Consequently, an in vitro photothermal irradiation experiment using NIR light indicated that DEX-GNRs exhibited a significant cell-killing efficacy, even with a lower concentration of Au and a low-power light source.

For the synthesis of biocompatible photothermal agents, gold nanorod-embedded polymeric nanoparticles (GPNs) were synthesized using a nanoprecipitation method. Uniform gold nanorods (GNRs), which are sensitive to a photothermal effect by near-infrared (NIR) light, with an aspect ratio of 4.0 were synthesized by a seed-mediated growth method. The hydroxyl groups of polycaprolactone diol (PCL diOH) were modified by esterification with mercaptopropionic acid to give a dithiol (polycaprolactone dithiol, PCL diSH) as a phase transfer and capping agent. Subsequently, hexadecyltrimethylammonium bromide (CTAB), a stabilizer of GNRs, was exchanged and/or removed by PCL diSH. PCL diSH-coated GNRs were further wrapped in a hydrophilic polymer, Pluronic F127, as a stabilizer. These newly formulated GPNs exhibit excellent stability in water and a maximum absorbance in the NIR region indicating a highly efficient surface plasmon resonance effect, phenomena useful for photothermal agents.

We fabricate the high-performance probes based on Au nanoparticles (AuNP) for detection of live cancer cell. AuNP were synthesized with narrow sized distribution (ca. 10 nm) by Au salt reduction method and deposited onto the aminated substrate as a cross-linker and hot spot. Herein, AuNP has enabled the easy and efficient immobilization of the antibody (Cetuximab), which can selectively interact with epidermal growth factor receptor (EGFR) on the surface of epidermal cancer, as detecting moiety onto the AuNP-deposited substrate without nanolithography process. After conjugation of Cetuximab with AuNP-deposited substrate, Cetuximab-conjugated probe as a live cancer cell detector (LCCD) could detect EGFR-highexpressed A431 cells related to epithelial cancer with 54-times larger specificity and sensitivity in comparison with EGFR-deficient MCF7 cells. This implies that AuNP-based probes demonstrate abundant potentials for detection and separation of small biomolecules, cells and other chemicals.