Surpassing sensitivity limits in liquid biopsy.

Attenuation of cell-free DNA clearance in vivo is an alternative strategy to maximize recovery.

Construction of mouse cochlin mutants with different GAG-binding specificities and their use for immunohistochemistry.

Glycosaminoglycan (GAG) is a polysaccharide present on the cell surface as an extracellular matrix component, and is composed of repeating disaccharide units consisting of an amino sugar and uronic acid except in the case of the keratan sulfate. Sulfated GAGs, such as heparan sulfate, heparin, and chondroitin sulfate mediate signal transduction of growth factors, and their functions vary with the type and degree of sulfated modification. We have previously identified human and mouse cochlins as proteins that bind to sulfated GAGs. Here, we prepared a recombinant cochlin fused to human IgG-Fc or Protein A at the C-terminus as a detection and purification tag and investigated the ligand specificity of cochlin. We found that cochlin can be used as a specific probe for highly sulfated heparan sulfate and chondroitin sulfate E. We then used mutant analysis to identify the mechanism by which cochlin recognizes GAGs and developed a GAG detection system using cochlin. Interestingly, a mutant lacking the vWA2 domain bound to various types of GAGs. The N-terminal amino acid residues of cochlin contributed to its binding to heparin. Pathological specimens from human myocarditis patients were stained with a cochlin-Fc mutant. The results showed that both tryptase-positive and tryptase-negative mast cells were stained with this mutant. The identification of detailed modification patterns of GAGs is an important method to elucidate the molecular mechanisms of various diseases. The method developed for evaluating the expression of highly sulfated GAGs will help understand the biological and pathological importance of sulfated GAGs in the future.

Impedimetric Detection of Calreticulin by a Disposable Immunosensor Modified with a Single-Walled Carbon Nanotube-Conducting Polymer Nanocomposite.

A label-free impedimetric immunosensing system was constructed for ultrasensitive determination of the calreticulin (CALR) biological marker in human serum samples utilizing an electrochemical impedance spectroscopy analysis technique for the first time. The new biosensor fabrication procedure consisted of electrodeposition of single-walled carbon nanotubes (SWCNTs) incorporating polymerization of an oxiran-2-yl methyl 3-(1H-pyrrol-1-yl) propanoate monomer (Pepx) onto a low-cost and disposable indium tin oxide (ITO) electrode. The SWCNTs-PPepx nanocomposite layer was prepared onto the ITO after the one-step fabrication procedure. The fabrication procedure of the immunosensor and the characteristic biomolecular interactions between the anti-CALR and CALR were characterized by electrochemical analysis and morphological monitoring techniques. Under optimum conditions, the proposed biosensor was responsive to CALR concentrations over the detection ranges of 0.015-60 pg/mL linearly, and it had a very low detection limit (4.6 fg/mL) and a favorable sensitivity (0.43 kΩ pg-1 mL cm-2). The reliability of the biosensor system in clinical analysis was investigated by successful quantification of CALR levels in human serum. Moreover, the repeatability and reproducibility results of the biosensor were evaluated by using Dixon, Grubbs, T-test, and F-tests. Consequently, the proposed biosensor was a promising method for scientific, rapid, and successful analysis of CALR in human serum samples.

A sensitive electrochemical platform integrated with a 3D graphene aerogel for point-of-care testing for tumor markers.

Point-of-care testing (POCT) of tumor markers, such as alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA), can be used for the early diagnosis of cancer. In this paper, a highly sensitive electrochemical immuno-biochip based on a porous three-dimensional graphene aerogel (3D-GA) is presented to detect multiple tumor biomarkers and exosomes. The 3D-GA was prepared via in situ chemical reduction of graphene oxide with L-ascorbic acid and then dehydration by freeze-drying. The obtained 3D-GA exhibits a large specific surface area of 125.3 m2 g-1 due to its intrinsic 3D porous architecture. After chemical activation and modification of the 3D-GA, the prepared microfluidic biochip can be used for detecting various tumor markers in liquid samples via electrochemical impedance spectroscopy (EIS). The electrochemical platform with only 5 µL sample achieved a broad detection range of 1.0 × 10-8-1.0 × 10-5 and 1.0 × 10-8-5.0 × 10-4 mg mL-1 for AFP and CEA, respectively, and a low limit of detection (LOD) of 7.9 and 6.2 pg mL-1 for AFP and CEA respectively, which was much better than the outcomes of many other reports. Moreover, the biochip determined the tumor cell-derived exosomes with a low LOD of 10 particles per µL in the PBS solution and an average recovery rate of ∼90% in the diluted serum.

Exploration of the Value of Combined UA, IL-6, and fPSA/tPSA in the Diagnosis of Prostate Cancer.

Objective: To investigate the differences in uric acid (UA), interleukin-6 (IL-6), and free prostatic-specific antigen (fPSA)/total prostatic-specific antigen (tPSA) (F/T) between patients with and without prostate cancer (PCa) in order to discover the value of the three indicators in improving PCa diagnostic accuracy. Methods: Patients with pathologically diagnosed PCa (PCa group, n = 25), patients with other benign prostate diseases (benign group, n = 25), and men who underwent normal physical examination (control group, n = 25) at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between October 2020 and January 2021 were included. The serum UA, IL-6, and F/T levels of participants in the three groups were measured, and the measured data were statistically analyzed. Results: There were statistically significant differences in IL-6 and F/T among the three groups (all P < 0.05), but there were no statistically significant differences in UA (P > 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) for the three indicators was, respectively, as follows: PCa group-benign group 0.5416, 0.6776, and 0.6832; PCa group-control group 0.5432, 0.9536, and 0.9887; and benign group-control group 0.5000, 0.8784, and 0.9456. Logistic regression analysis indicated that IL-6 and F/T were independent predictors of PCa, with AUCs of 0.6776 and 0.6832, respectively, and a combined accuracy of 72.0%. Conclusion: These results suggest that IL-6 and F/T have a good detection effect for PCa screening. Compared with the detection of F/T alone, the combined detection of IL-6 and F/T can improve the diagnosis rate of PCa to a certain extent, providing effective guidance for the clinical diagnosis and treatment of patients. The value of UA needs to be further studied, and its feasibility in the diagnosis of PCa needs to be further explored.

A review on the treatment of multiple myeloma with small molecular agents in the past five years.

Multiple myeloma is currently incurable, and the incidence rate is increasing year by year worldwide. Although in recent years the combined treatment plan based on proteasome inhibitors and immunomodulatory drugs has greatly improved the treatment effect of multiple myeloma, most patients still relapse and become resistant to current treatments. To solve this problem, scientists are committed to developing drugs with higher specificity, such as iberdomide, which is highly specific to ikaros and aiolos. This review aims to focus on the small molecular agents that are being researched/clinically used for the treatment of multiple myeloma, including the target mechanism, structure-activity relationship and application prospects of small molecular agents.

Simultaneous analysis of serum α2,3-linked sialylation and core-type fucosylation of prostate-specific antigen for the detection of high-grade prostate cancer.

BACKGROUND: Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay system can analyse α2,3-linked sialylated PSA (α2,3-Sia-PSA) and α1,6-linked fucosylated PSA (α1,6-Fuc-PSA) using different lectins, Mackkia amurensis agglutinin and Pholiota squarrosa lectin, respectively. Here, we investigated the diagnostic value of simultaneous analysis of α2,3-Sia-PSA and α1,6-Fuc-PSA for the detection of HGPC. METHODS: Men with serum PSA levels of 4-20 ng/mL who underwent prostate biopsy were included. The model to predict HGPC (Gleason grade ≥2) was constructed by multivariate logistic regression analysis, in combination with α2,3-Sia-PSA and α1,6-Fuc-PSA (SF index). RESULTS: In the development cohort (n = 150), the SF index showed good discrimination for HGPC (area under the receiver-operating curve (AUC) 0.842; 95% confidence interval (CI) 0.782-0.903), compared to the single PSA test (AUC 0.632, 95% CI 0.543-0.721), α2,3-Sia-PSA (AUC 0.711, 95% CI 0.629-0.793) and α1,6-Fuc-PSA (AUC 0.738, 95% CI 0.657-0.819). Decision-curve analysis showed the superior benefit of the SF index. In the validation cohort (n = 57), the SF index showed good discrimination for HGPC (AUC 0.769, 95% CI 0.643-0.895). CONCLUSIONS: The SF index could differentiate HGPC, providing useful information for decision making for prostate biopsy in men with abnormal PSA levels.

CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma.

Recent studies have reported that MLST8 is upregulated in many malignant tumors. Nevertheless, the underlying molecular mechanism is still unclear. The aim of this work was to investigate how MLST8 contributes to the development and progression of clear cell renal cell carcinoma (ccRCC). MLST8 is an oncogenic protein in the TCGA database and ccRCC clinical specimens. We also ascertain that MLST8 interacts with FBXW7, which was universally regarded as an E3 ubiquitin ligase. MLST8 can be degraded and ubiquitinated by tumor suppressor FBXW7. FBXW7 recognizes a consensus motif (T/S) PXX (S/T/D/E) of MLST8 and triggers MLST8 degradation via the ubiquitin-proteasome pathway. Strikingly, the activated cyclin dependent kinase 1 (CDK1) kinase engages in the MLST8 phosphorylation required for FBXW7-mediated degradation. In vitro, we further prove that MLST8 is an essential mediator of FBXW7 inactivation-induced tumor growth, migration, and invasion. Furthermore, the MLST8 and FBXW7 proteins are negatively correlated in human renal cancer specimens. Our findings suggest that MLST8 is a putative oncogene that functions via interaction with FBXW7, and inhibition MLST8 could be a potential future target in ccRCC treatment.

Expression of N-Terminal-Deficient E-Cadherin Protein in Invasive Lobular Carcinoma of the Breast.

Invasive lobular carcinoma (ILC) of the breast is characterized by the discohesive growth of tumor cells, which is mainly associated with the complete loss of E-cadherin (E-cad) expression. However, some aberrant expression patterns of E-cad protein that are inconsistent with their morphologies have been reported in ILC. We report herein ILC cases expressing a new type of abnormal E-cad protein that lacks the N-terminal domain, but conserves the C-terminal domain on the cell membrane. Immunohistochemical staining of 299 ILC cases using specific antibodies against the N-terminal or C-terminal region of E-cad revealed that 227 (76%) cases showed loss of the membranous expression of both terminuses (N-/C-) and 72 (24%) cases showed expression of only the C-terminus (N-/C+). In all cases, the expression of p120-catenin and ß-catenin coincided with the expression of the C-terminus of E-cad. Clinicopathologic analysis revealed that N-/C+ expression in ILC cells was significantly associated with the histologic subtype (especially mixed-type ILC with another histologic type) and immunohistochemical molecular subtype (especially the triple-negative subtype), but not with prognostic factors (pT or pN). In addition, 12 of 15 cases (80%) with aberrant cytoplasmic localization of the N-terminal of E-cad showed diffuse membranous expression of the C-terminal domain. Additional immunohistochemistry using an antibody recognizing the extracellular juxtamembrane region showed that 28 (39%) of the N-/C+ cases had lost membranous expression, suggesting diversity in the deletion pattern of the N-terminal region. Our findings provide a novel mechanism for the loss of E-cad function because of N-terminal-deficient E-cad protein in ILC.

From Raman to SESORRS: moving deeper into cancer detection and treatment monitoring.

Raman spectroscopy is a non-invasive technique that allows specific chemical information to be obtained from various types of sample. The detailed molecular information that is present in Raman spectra permits monitoring of biochemical changes that occur in diseases, such as cancer, and can be used for the early detection and diagnosis of the disease, for monitoring treatment, and to distinguish between cancerous and non-cancerous biological samples. Several techniques have been developed to enhance the capabilities of Raman spectroscopy by improving detection sensitivity, reducing imaging times and increasing the potential applicability for in vivo analysis. The different Raman techniques each have their own advantages that can accommodate the alternative detection formats, allowing the techniques to be applied in several ways for the detection and diagnosis of cancer. This feature article discusses the various forms of Raman spectroscopy, how they have been applied for cancer detection, and the adaptation of the techniques towards their use for in vivo cancer detection and in clinical diagnostics. Despite the advances in Raman spectroscopy, the clinical application of the technique is still limited and certain challenges must be overcome to enable clinical translation. We provide an outlook on the future of the techniques in this area and what we believe is required to allow the potential of Raman spectroscopy to be achieved for clinical cancer diagnostics.

Prognostic value of CD169-positive macrophages in various tumors: a meta-analysis.

The study aimed to evaluate the prognostic value of CD169 expression in tumor-infiltrating macrophages from regional lymph nodes (RLN) in various tumors. In order to identify eligible articles, PubMed, EMBASE, Web of Science, and Cochrane Library were used to conduct a systematic search. Pooled hazard ratios (HRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were adopted to assess the relationship between CD169 expression and overall survival (OS) and clinicopathological characteristics. Ten studies, including eleven cohorts with 1699 patients, were enrolled. We found that high CD169+ expression in tumor-infiltrating macrophages from RLN was associated with a favorable OS (HR = 0.56, 95%CI: 0.39-0.79, P = 0.001). Subgroup analysis showed that high CD169+ expression had more predictive power in digestive system tumors (HR = 0.52, 95%CI: 0.42-0.67, <0.001). In addition, high CD169 expression was significantly linked with lymph node metastasis (OR = 0.66, 95%CI: 0.47-0.94, P = 0.020) and TNM stage (OR = 0.62, 95%CI: 0.48-0.80, P < 0.001). High CD169 expression in tumor-infiltrating macrophages from RLN was correlated with favorable survival outcome in patients with malignancies. CD169 may be a novel and effective prognostic marker, especially for digestive system tumors.

Enolase 1, a Moonlighting Protein, as a Potential Target for Cancer Treatment.

Enolase 1 (ENO1) is a moonlighting protein, function as a glycolysis enzyme, a plasminogen receptor and a DNA binding protein. ENO1 play an important role in the process of cancer development. The transcription, translation, post-translational modifying activities and the immunoregulatory role of ENO1 at the cancer development is receiving increasing attention. Some function model studies have shown that ENO1 is a potential target for cancer treatment. In this review, we provide a comprehensive overview of the characterization, function, related transduction cascades of ENO1 and its roles in the pathophysiology of cancers, which is a consequence of ENO1 signaling dysregulation. And the development of novels anticancer agents that targets ENO1 may provide a more attractive option for the treatment of cancers. The data of sarcoma and functional cancer models indicates that ENO1 may become a new potential target for anticancer therapy.

High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and Weighted Gene Coexpression Network Analysis (WGCNA).

Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.

Recent advances in nanomaterials-based electrochemical immunosensors and aptasensors for HER2 assessment in breast cancer.

Human epidermal growth factor receptor 2 (HER2) is one of the key molecular targets in breast cancer pathogenesis. Overexpression and/or amplification of HER2 in approximately 15-20% of breast cancer patients is associated with high mortality and poor prognosis. Accumulating evidence shows that accurate and sensitive detection of HER2 improves the survival outcomes for HER2-positive breast cancer patients from targeted therapies. The current methods of clinical determination of HER2 expression levels are based on slide-based assays that rely on invasively collected primary tumours. Alternatively, ELISA-based detection of the shredded HER2 extracellular domain (HER2-ECD) of has been suggested as a surrogate method for monitoring disease progress and treatment response in breast cancer patients. In the past decade, biosensors have emerged as an alternative modality for the detection of circulating HER2-ECD in human serum samples. In particular, electrochemical biosensors based on nanomaterials and antibodies and aptamers have been increasingly developed as promising tools for rapid, sensitive, and cost-effective detection of HER2-ECD. These biosensors harness the high affinity and specificity of antibodies and aptamers, and unique conductive properties, biocompatibility, large surface area, and chemical stability of nanomaterials for selective and sensitive assessment of the HER2. This review provides an overview of the recent advances in the application of nanomaterials-based immunosensors and aptasensors for detection of circulating HER2-ECD. In particular, various electrochemical techniques, detection approaches, and nanomaterials are discussed. Further, analytical figures of merit of various HER2 immunosensors and aptasensors are compared. Finally, possible challenges and potential opportunities for biosensor-based detection of HER2-ECD are discussed.

Dual-modality loop-mediated isothermal amplification for pretreatment-free detection of Septin9 methylated DNA in colorectal cancer.

Currently, the determination of DNA methylation is still a challenge due to the limited efficiency of enrichment, bisulfite modification, and detection. In this study, a dual-modality loop-mediated isothermal amplification integrated with magnetic bead isolation is  proposed for the determination of methylated Septin9 gene in colorectal cancer. Magnetic beads modified with anti-methyl cytosine antibody were prepared for fast enrichment of methylated DNA through specific immunoaffinity (30 min). One-pot real-time fluorescence and colorimetric loop-mediated isothermal amplification were simultaneously developed for detecting methylated Septin9 gene (60 min). The real-time fluorescence generating by SYTO-9 dye (excitation: 470 nm and emission: 525 nm) and pH indicator (neutral red) was used for quantitative and visualized detection of methylated DNA. This method was demonstrated to detect methylated DNA from HCT 116 cells ranging from 2 to 0.02 ng/µL with a limit of detection of 0.02 ± 0.002 ng/µL (RSD: 9.75%). This method also could discriminate methylated Septin9 in 0.1% HCT 116 cells (RSD: 6.60%), suggesting its high specificity and sensitivity. The feasibility of this assay was further evaluated by clinical plasma samples from 20 colorectal cancer patients and 20 healthy controls, which shows the potential application in simple, low cost, quantitative, and visualized detection of methylated nucleic acids. A dual-modality loop-mediated isothermal amplification (LAMP) integrated with immuno-magnetic beads (IMB) enrichment was proposed for the determination of methylated Septin9 gene in colorectal cancer (CRC).

The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state.

The Hsp90 chaperone promotes folding and activation of hundreds of client proteins in the cell through an ATP-dependent conformational cycle guided by distinct cochaperone regulators. The FKBP51 immunophilin binds Hsp90 with its tetratricopeptide repeat (TPR) domain and catalyzes peptidyl-prolyl isomerase (PPIase) activity during folding of kinases, nuclear receptors, and tau. Here we determined the cryoelectron microscopy (cryo-EM) structure of the human Hsp90:FKBP51:p23 complex to 3.3 Å, which, together with mutagenesis and crosslinking analyses, reveals the basis for cochaperone binding to Hsp90 during client maturation. A helix extension in the TPR functions as a key recognition element, interacting across the Hsp90 C-terminal dimer interface presented in the closed, ATP conformation. The PPIase domain is positioned along the middle domain, adjacent to Hsp90 client binding sites, whereas a single p23 makes stabilizing interactions with the N-terminal dimer. With this architecture, FKBP51 is positioned to act on specific client residues presented during Hsp90-catalyzed remodeling.

MUC1: Structure, Function, and Clinic Application in Epithelial Cancers.

The transmembrane glycoprotein mucin 1 (MUC1) is a mucin family member that has different functions in normal and cancer cells. Owing to its structural and biochemical properties, MUC1 can act as a lubricant, moisturizer, and physical barrier in normal cells. However, in cancer cells, MUC1 often undergoes aberrant glycosylation and overexpression. It is involved in cancer invasion, metastasis, angiogenesis, and apoptosis by virtue of its participation in intracellular signaling processes and the regulation of related biomolecules. This review introduces the biological structure and different roles of MUC1 in normal and cancer cells and the regulatory mechanisms governing these roles. It also evaluates current research progress and the clinical applications of MUC1 in cancer therapy based on its characteristics.

Recent advances in proteomics and its implications in pituitary endocrine disorders.

Pituitary adenoma is considered as one of the most frequent intracranial tumors having salient impact on human health such as mass effects, hypopituitarism and visual defects etc. During the past few decades, there has been enormous advancement in mass spectrometry (MS)-based proteomics. However, very little is known about the molecular pathogenesis of pituitary adenomas in the context of proteomics. In this review article, we have focused on the provenance of pituitary tumors and their pathogenesis with the help of MS-based proteomics approaches. Recent advancements in quantitative proteomic approaches are outlined here that would be useful in the near pituitary adenoma proteomics research. This review discusses the enormous potential of pituitary adenomas research through proteomics with a common aim of deciphering disease pathobiology and identifying the work done in studying pituitary tumors during past decade.

Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening : A Diagnostic Test Accuracy Study.

BACKGROUND: The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement. OBJECTIVE: To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT. DESIGN: Diagnostic test accuracy study. SETTING: Colonoscopy-controlled series. PARTICIPANTS: Persons (n = 1284) from a screening (n = 1038) and referral (n = 246) population were classified by their most advanced lesion (CRC [n = 47], advanced adenoma [n = 135], advanced serrated polyp [n = 30], nonadvanced adenoma [n = 250], and nonadvanced serrated polyp [n = 53]), along with control participants (n = 769). MEASUREMENTS: Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity. RESULTS: The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT (P = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) (P = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT. LIMITATION: Study population is enriched with persons from a referral population. CONCLUSION: Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for population-based CRC screening. A prospective screening trial is in preparation. PRIMARY FUNDING SOURCE: Stand Up to Cancer/Dutch Cancer Society, Dutch Digestive Foundation, and HealthHolland.

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.