Geometrically encoded SERS nanobarcodes for the logical detection of nasopharyngeal carcinoma-related progression biomarkers.

The limited availability of nasopharyngeal carcinoma-related progression biomarker array kits that offer physicians comprehensive information is disadvantageous for monitoring cancer progression. To develop a biomarker array kit, systematic identification and differentiation of a large number of distinct molecular surface-enhanced Raman scattering (SERS) reporters with high spectral temporal resolution is a major challenge. To address this unmet need, we use the chemistry of metal carbonyls to construct a series of unique SERS reporters with the potential to provide logical and highly multiplex information during testing. In this study, we report that geometric control over metal carbonyls on nanotags can produce 14 distinct barcodes that can be decoded unambiguously using commercial Raman spectroscopy. These metal carbonyl nanobarcodes are tested on human blood samples and show strong sensitivity (0.07 ng/mL limit of detection, average CV of 6.1% and >92% degree of recovery) and multiplexing capabilities for MMPs.

Photoinduced Enhanced Raman Probe for Use in Highly Specific and Sensitive Imaging for Tyrosine Dimerization in Inflammatory Cells.

A background-free photoinduced enhanced Raman (PIER) probe for highly sensitive detection of tyrosine dimerization process due to oxidative reaction in inflammatory cells is presented. The PIER probe could monitor oxidative reaction in real time by producing time-resolved spectral with discrete changes in Raman intensity. To the best of our knowledge, this is the first report on C≡C probes with PIER and vastly improved Raman activity. These results will contribute to the cutting edge of development of stable and highly sensitive chemical imaging technology.

Operando characterization of chemical reactions in single living cells using SERS.

Detection of chemical reactions in living cells is critical in understanding physiological metabolic processes in the context of nanomedicine. Carbon monoxide (CO) is one of the important gaseous signaling molecules. Surface-enhanced Raman spectroscopy (SERS)-based CO-releasing nanoparticles (CORN) is utilized to investigate the chemical reaction of CO delivery in live cells. Using SERS CORN, carbonyl dissociation from CORN-Ag-CpW(CO)3 to CORN-Ag-CpW(CO)2 in live cells is observed. The subsequent irreversible degradation to CO-free CORN is a consequence of oxidative stress in cells. This observation affirms the step transition of CORN-Ag-CpW(CO)3 in cellular: CORN-Ag-CpW(CO)3 first proceeds via a direct loss of one CO followed by a oxidative decomposition giving rise to CORN-Ag-WO3 and as well as the release of one equivalents of CO. Importantly, the decarbonylation process can be correlated with the level of inflammatory biomarkers. For the first time, we provide unambiguous evidence for the steps transition of CO-release mechanism in cellular.

Reversible detection of phosphorylation and dephosphorylation by tip-enhanced Raman spectroscopy using a cyclopentadienyl ruthenium nanotag functionalized tip.

The detection of cancer invasion is crucial for diagnosis. In this report, we employed a TERS tip and SERS nanotags to create a cell signaling based nano-sensing system. This system is capable of creating a reversible phosphorylation/de-phosphorylation cycle for TERS measurement. The reversible TERS sensing is then paired with a downstream binding domain, Src homology region 2 (SH2), which is associated with the cell signaling for cancer cell invasion. Such a system offers the advantages of convenient detection of nanotags and high sensitivity as validated in a cell model.

Lymphocyte Antigen 6 Complex, Locus C+ Monocytes and Kupffer Cells Orchestrate Liver Immune Responses Against Hepatitis B Virus in Mice.

To understand the mechanism(s) of age-dependent outcomes of hepatitis B virus (HBV) infection in humans, we previously established an age-related HBV mouse model in which 6-week-old (N6W) C3H/HeN mice exhibited virus tolerance whereas 12-week-old (N12W) counterparts presented virus clearance. By investigating the hepatic myeloid cell dynamics in mice of these two ages, we aim to identify factors associated with HBV clearance. C3H/HeN mice were transfected with an HBV plasmid by hydrodynamic injection. Serum HBV markers were monitored weekly. Hepatic leucocyte populations and their cytokine/chemokine productions were examined at baseline, day 3 (D3), day 7 (D7), and day 14 after injection. C-C chemokine receptor type 2 (CCR2) antagonist and clodronate (CLD) were respectively administered to N12W and N6W mice to study the roles of lymphocyte antigen 6 complex, locus C (Ly6C)+ monocytes and Kupffer cells (KCs) in viral clearance. N12W mice had a significantly higher number of TNF-α-secreting Ly6C+ monocytes and fewer IL-10-secreting KCs at D3 in the liver than their younger N6W counterparts after HBV transfection. In addition, the elevated number of interferon-γ+ TNF-α+ CD8+ T cells at D7 was only seen in the older cohort. The enhanced Ly6C+ monocyte induction in N12W mice resulted from elevated C-C motif chemokine ligand 2 (CCL2) secretion by hepatocytes. CCR2 antagonist administration hampered Ly6C+ monocyte recruitment and degree of KC reduction and delayed HBV clearance in N12W animals. Depletion of KCs by CLD liposomes enhanced Ly6C+ monocyte recruitment and accelerated HBV clearance in N6W mice. Conclusions: Ly6C+ monocytes and KCs may, respectively, represent the resistance and tolerance arms of host defenses. These two cell types play an essential role in determining HBV clearance/tolerance. Manipulation of these cells is a promising avenue for immunotherapy of HBV-related liver diseases.