Comparative hyperthermia effects of silica-gold nanoshells with different surface coverage of gold clusters on epithelial tumor 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 propertiesope

Strategies for using nanoprobes to perceive and treat cancer activity: a review

Nanomedicine has seen a significant increase in research on stimuli-responsive activatable nanoprobes for tumor-specific delivery and diagnosis. The tumor microenvironment has particular characteristics that can be exploited to implement therapeutic strategies based on disparities between normal tissues and tumor tissues, including differences in pH, oxygenation, enzymatic expression, gene activation/inactivation, and vasculature. The nanocarriers of activatable nanoparticles maintain their structure while circulating in the body and, upon reaching the tumor site, are altered by unique tumoral stimuli, leading to the release of a drug or other agent. This review demonstrates the latest achievements in the use of internal stimuli-responsive, activatable nanoparticles with respect to unique design strategies and applications.ope

Amplification of T2 relaxation rate in MR imaging via tuning magnetic seed nanoparticles

We describe the preparation of superparamagnetic nanoclusters (SNCs) by fine-tuning of the seed Fe3O4 nanoparticle sizes to enhance and their T2 relaxivity can be increased by > 4-fold. Therefore, with 11 nm seed core and PVA coating, SNC-11 exhibit a higher T2 relaxivity than other cluster condition. So fabricating the cluster, seed size is the most important influence the T2 relaxivity. As well as, in vitro cellular imaging results demonstrated the strong potential of SNCs for clinical applications by targeting affinity. According to the experiments, with 11 nm seed core and PVA coating, SNC-11 exhibited the highest T2 relaxivity of 454 mM-1s-1 due to the strong seed size effect on their magnetic sensitivity, indicating superior magnetic resonance (MR) contrast efficiency. Further in vitro cellular imaging results demonstrated the strong potential of SNCs for clinical applications.ope

Ligation-free isothermal nucleic acid amplification

In this study, we uncover a ligation-free DNA extension method in two adjacent fragmented probes, which are hybridized to target RNA, for developing a ligation-free nucleic acid amplification reaction. In this reaction, DNA elongation occurs from a forward probe to a phosphorothioated-hairpin probe in the presence of target RNA regardless of ligation. The second DNA elongation then occurs simultaneously at the nick site of the phosphorothioated probe and the self-priming region. Therefore, the binding site of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 12a is repeatedly amplified, inducing a fluorescence signal in the presence of CRISPR-Cas12a. This ligation-free isothermal gene amplification method enables the detection of target RNA with 49.2 fM sensitivity. Moreover, two types of mRNA detection are feasible, thus, demonstrating the potential of this method for cancer companion diagnostics. Notably, the proposed method also demonstrates efficacy when applied for the detection of mRNA extracted from human cells and tumor-bearing mouse tissue and urine samples. Hence, this newly developed ligation-free isothermal nucleic acid amplification system is expected to be widely used in a variety of gene detection platforms.ope

Discrimination of single nucleotide mismatches using a scalable, flexible, and transparent three-dimensional nanostructure-based plasmonic miRNA sensor with high sensitivity

Localized surface plasmon resonance (LSPR) biosensors have attracted much interest due to their capacity for multiplexing, miniaturization, and high performance, which offers the potential for their integration into lab-on-a-chip platforms for point-of-care (POC) diagnostics. The need for microRNA (miRNA)-sensing platforms is particularly urgent because miRNAs are key regulators and biomarkers in numerous pathological processes and diseases. Unfortunately, however, development of such miRNA-sensing platforms has not yet been achieved. In order to realize the detection of these important biomarkers, there has been an increasing demand for POC-sensing platforms that enable label-free quantification with low sample consumption, good sensitivity, real-time responsiveness, and high throughput. Here, we developed a highly specific, sensitive LSPR miRNA-sensing platform on a flexible, scalable plasmonic nanostructure to enable single-base mismatch discrimination and attomole detection of miRNAs in clinically relevant samples. The hairpin probe contained a locked nucleic acid (LNA) that enabled the discrimination of single base mismatches based on differences in melting temperatures of perfectly matched or single base mismatched miRNAs when they formed base pairs with probes. In addition, through hybridization induced signal amplification based on precipitate formation on the gold surface through the enzyme reaction, we observed a dramatic LSPR peak shift, which enabled attomole detection. Additionally, our LSPR miRNA sensor enabled the detection of miR-200a-3p in total RNA extracts from primary cancer cell lines without purification or labeling of the miRNA. This label-free and highly specific miRNA sensing platform may have applications in POC cancer diagnostics without the need for gene amplification.ope

Isolation of RNA Aptamers Targeting HER-2-overexpressing Breast Cancer Cells Using Cell-SELEX

Ligand molecules that can recognize and interact with cancer cell surface marker proteins with high affinity and specificity should greatly aid the development of novel cancer diagnostics and therapeutics. HER-2/ErbB2/Neu (HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves as both a useful biomarker and a therapeutic target for breast cancer. In this study, we aimed to isolate RNA aptamers that specifically bind to a HER-2-overexpressing human breast cancer cell line, SK-BR-3, using Cell-SELEX strategy. The selected aptamers showed strong affinity to SK-BR-3, but not to MDAMB- 231, a HER-2-underexpressing breast cancer cell line. In addition, we confirmed the specific targeting of HER-2 receptor by aptamers using an unrelated mouse cell line overexpressing human HER-2 receptor. The HER-2-targeting RNA aptamers could become a useful reagent for the development of breast cancer diagnostics and therapeuticsope

Preparation and Characterization of Magnetized Microneedles for Magnetic Resonance Molecular Imaging

In this study, magnetized microneedles (MMNs) that contain herceptin conjugated to iron oxide nanoparticles were manufactured by low temperature process technology and its effects on magnetic resonance (MR) molecular imaging were investigated. The results showed that after the MMNs were manufactured, changes in morphology and magnetic properties were not observed and more than 90% of the skin permeability and cell viability were confirmed and dramatic signal intensity changes of MMNs containing herceptin were confirmed more than 30% on magnetic resonance imaging measurements. In conclusion, it is expected that MMNs containing herceptin have an essential role as a base technology in the field of MR molecular imaging, which can diagnose and therapeutic through transdermal drug delivery system.ope

Inner structure- and surface-controlled hollow MnO nanocubes for high sensitive MR imaging contrast effect

Manganese oxide (MnO) nanocubes were fabricated and their surface were modified by ligand encapsulation or ligand exchange, to render them water-soluble. And then, MnO formed the hollow structure by etching using acidic solution (phthalate buffer, pH 4.0). Depending on the ligand of the MnO surface, it increases the interaction between MnO and water molecules. Also, the hollow structure of MnO, as well as the ligand, can greatly enhance the accessibility of water molecules to metal ions by surface area-to-volume ratio. These factors provide high R1 relaxation, leading to strong T1 MRI signal. We have confirmed T1-weighted MR contrast effect using 4-kinds of MnO nanocubes (MnOEn, MnOEnHo, MnOEx and MnOExHo). They showed enough a MR contrast effect and biocompatibility. Especially, among them, MnOExHo exhibited high T1 relaxivity (r1) (6.02 mM-1 s-1), even about 1.5 times higher sensitivity than commercial T1 MR contrast agents. In vitro/in vivo studies have shown that MnOExHo provides highly sensitive T1-weighted MR imaging, thereby improving diagnostic visibility at the disease site.ope

Facile Preparation of Pyrene-templated Hexagonal-shaped Gold Nanoplates

We have formulated hexagonal-shaped gold nanoplates in a single-step for photothermal therapy that gold ions to gold particles using pyrenyl dextran as reducible stabilizer and template. They exhibit anisotropic structure with broad surface plasmon resonance (SPR) band into near-infrared (NIR) spectrum enabling photothermal therapy. These gold nanoplates are also confirmed biocompatibility and high uptake efficiency due to binding with dextran molecules on the surface of gold nanoplates and cells. From in vitro phtothermal ablation study under NIR laser, gold nanoplates have the potential to use as photothermal agents.ope

T2-Weighted and Ultra-short TE Molecular Magnetic Resonance Imaging for Gastric Cancer Diagnosis using Polymer-based Magnetic Nanoparticles

Several recently developed technologies for molecular imaging have been applied to magnetic resonance (MR) imaging for cancer. In particular, various MR sequences with biocompatible polymer-based magnetic nanoparticles (pMNPs) have been applied for the MR imaging of cancer. However, there are several limitations to this approach, and passive contrast agents are not yet sufficiently targeted. This is a particular challenge for gastric cancer owing to the interference from stomach contents. Therefore, in this study we developed targeting contrast agent and assessed its feasibility for early gastric cancer diagnosis using a mouse model. Specifically, we synthesized pMNPs, which enable both T2-weighted (T2) and ultra-short TE (UTE) MR imaging using hyaluronic acid as the polymer, which binds to the receptor CD44, a recently identified biomarker of gastric cancer. Both MR sequences (T2, UTE) were analyzed with respect to imaging effects and targeting to the pMNPs. In vitro assessments showed no significant cytotoxicity of the pMNPs to MKN-45 and MKN-28 cells and confirmed the cellular uptake of the pMNPs. MR signal enhancement was identified after pMNPs injection to the mice, and the pMNPs gradually accumulated in the tumors. Based on the results, we suggest that pMNPs serve as useful probes for imaging stem-like cancer cells, and can further provide new possibilities by simultaneously confirming T1 and T2 MR imaging effects.ope